As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major h...As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major histological subtype of EC,and its incidence and mortality rates are decreasing globally.Due to the lack of specific early symptoms,ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis,and the incidence and mortality rates are still high in many countries,especially in China.Therefore,enormous challenges still exist in the management of ESCC,and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC.Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated,certain promising biomarkers are being investigated to facilitate clinical decision-making.With the advent and advancement of highthroughput technologies,such as genomics,proteomics and metabolomics,valuable biomarkers with high sensitivity,specificity and stability could be identified for ESCC.Herein,we aimed to determine the epidemiological features of ESCC in different regions of the world,especially in China,and focused on novel molecular biomarkers associated with ESCC screening,early diagnosis and prognosis prediction.展开更多
BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is ...BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.展开更多
In this editorial,we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.We focused on identifying risk factors for lymph node metastasis(LNM)in superfic...In this editorial,we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.We focused on identifying risk factors for lymph node metastasis(LNM)in superficial esophageal squamous cell carcinoma(SESCC)patients and how to construct a simple and reliable clinical prediction model to assess the risk of LNM in SESCC patients,thereby helping to guide the selection of an appropriate treatment plan.The current standard treatment for SESCC is radical esophagectomy with lymph node dissection.However,esophagectomy is associated with considerable morbidity and mortality.Endoscopic resection(ER)offers a safer and less invasive alternative to surgical resection and can enable the patient's quality of life to be maintained while providing a satisfactory outcome.However,since ER is a localized treatment that does not allow for lymph node dissection,the risk of LNM in SESCC limits the effectiveness of ER.Understanding LNM status can aid in determining whether patients with SESCC can be cured by ER without the need for additional esophagectomy.Previous studies have shown that tumor size,macroscopic type of tumor,degree of differentiation,depth of tumor invasion,and lymphovascular invasion are factors associated with LNM in patients with SESCC.In addition,tumor budding is commonly associated with LNM,recurrence,and distant metastasis,but this topic has been less covered in previous studies.By comprehensively evaluating the above risk factors for LNM,useful evidence can be obtained for doctors to select appropriate treatments for SESCC patients.展开更多
Objective:CD8+T cells are the key effector cells in the anti-tumor immune response.The mechanism underlying the infiltration of CD8+T cells in esophageal squamous cell carcinoma(ESCC)has not been clearly elucidated.Me...Objective:CD8+T cells are the key effector cells in the anti-tumor immune response.The mechanism underlying the infiltration of CD8+T cells in esophageal squamous cell carcinoma(ESCC)has not been clearly elucidated.Methods:Fresh ESCC tissues were collected and grouped according to the infiltration density of CD8+T cells.After the transcriptome sequencing on these samples and the combined analyses with The Cancer Genome Atlas(TCGA)ESCC data,a secreted protein DEFB1 was selected to explore its potential role in the infiltration of CD8+T cells.Bioinformatics analyses,histological verification and in vitro experiments were then performed.Results:DEFB1 was highly expressed in ESCC,and the high expression of DEFB1 was an independent risk factor for overall survival.Since the up-regulation or down-regulation of DEFB1 did not affect the proliferation,migration and apoptosis of ESCC cells,we speculated that the oncogenic effect of DEFB1 was achieved by regulating microenvironmental characteristics.Bioinformatics analyses suggested that DEFB1 might play a major role in the inflammatory response and anti-tumor immune response,and correlate to the infiltration of immature dendritic cell(imDC)in ESCC.Histological analyses further confirmed that there were less CD8+T cells infiltrated,less CD83+mature DC(mDC)infiltrated and more CD1a+imDC infiltrated in those ESCC samples with high expression of DEFB1.After the treatment with recombinant DEFB1 protein,the maturation of DC was hindered significantly,followed by the impairment of the killing effects of T cells in both 2D and 3D culture in vitro.Conclusions:Tumor-derived DEFB1 can inhibit the maturation of DC and weaken the function of CD8+T cells,accounting for the immune tolerance in ESCC.The role of DEFB1 in ESCC deserves further exploration.展开更多
In recent years,endoscopic resection,particularly endoscopic submucosal dis-section,has become increasingly popular in treating non-metastatic superficial esophageal squamous cell carcinoma(ESCC).In this evolving para...In recent years,endoscopic resection,particularly endoscopic submucosal dis-section,has become increasingly popular in treating non-metastatic superficial esophageal squamous cell carcinoma(ESCC).In this evolving paradigm,it is crucial to identify factors that predict higher rates of lymphatic invasion and poorer outcomes.Larger tumor size,deeper invasion,poorer differentiation,more infiltrative growth patterns(INF-c),higher-grade tumor budding,positive lymphovascular invasion,and certain biomarkers have been associated with lymph node metastasis and increased morbidity through retrospective reviews,leading to the construction of comprehensive nomograms for outcome prediction.If validated by future prospective studies,these nomograms would prove highly applicable in guiding the selection of treatment for superficial ESCC.展开更多
Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths globally.The increased mortality rate of ES...Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths globally.The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered,coupled with higher risk of metastasis,which is an exceedingly malignant charac-teristic of cancer,frequently leading to a high mortality rate.Unfortunately,there is currently no specific and effective marker to predict and treat metastasis in ESCC.MicroRNAs(miRNAs)are a class of small non-coding RNA molecules,approximately 22 nucleotides in length.miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence,progression,and prognosis of cancer.Here,we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis,and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors.This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis,with the ultimate aim of reducing the mortality rate among patients with ESCC.展开更多
Esophageal squamous cell carcinoma(ESCC)is the most common histological type of esophageal cancer with a poor prognosis.Early diagnosis and prognosis assessment are crucial for improving the survival rate of ESCC pati...Esophageal squamous cell carcinoma(ESCC)is the most common histological type of esophageal cancer with a poor prognosis.Early diagnosis and prognosis assessment are crucial for improving the survival rate of ESCC patients.With the advancement of artificial intelligence(AI)technology and the proliferation of medical digital information,AI has demonstrated promising sensitivity and accuracy in assisting precise detection,treatment decision-making,and prognosis assessment of ESCC.It has become a unique opportunity to enhance comprehen-sive clinical management of ESCC in the era of precision oncology.This review examines how AI is applied to the diagnosis,treatment,and prognosis assessment of ESCC in the era of precision oncology,and analyzes the challenges and potential opportunities that AI faces in clinical translation.Through insights into future prospects,it is hoped that this review will contribute to the real-world application of AI in future clinical settings,ultimately alleviating the disease burden caused by ESCC.展开更多
BACKGROUND Immunochemotherapy involving the combination of programmed cell death 1/programmed cell death ligand 1 inhibitors with chemotherapy has advanced the treatment of locally advanced esophageal squamous cell ca...BACKGROUND Immunochemotherapy involving the combination of programmed cell death 1/programmed cell death ligand 1 inhibitors with chemotherapy has advanced the treatment of locally advanced esophageal squamous cell carcinoma(ESCC).The use of corticosteroids as pretreatment might reduce immunotherapy efficacy.AIM To investigate the impact of baseline corticosteroid use on neoadjuvant immunochemotherapy(nIC)outcomes in locally advanced ESCC patients.METHODS Patients with locally advanced ESCC who received nIC at Sun Yat-sen University Cancer Center and the Third Affiliated Hospital of Sun Yat-sen University were included.Patients were divided into dexamethasone and antihistamine groups on the basis of the administered pretreatment.Antiallergic efficacy and safety were evaluated,as well as its impact on short-term efficacy[complete pathological response(pCR),major pathological response(MPR)]and long-term efficacy[overall survival(OS),progression-free survival(PFS)]of nIC.RESULTS From September 2019 to September 2023,142 patients were analyzed.No severe treatment-related adverse events or deaths were observed.Allergy occurrence was greater in the antihistamine group(P=0.014).Short-term efficacy was not significantly different:The pCR rates were 29.9%and 40.0%,and the MPR rates were 57.9%and 65.7%in the dexamethasone and antihistamine groups,respectively.The long-term efficacy was not significantly different:The 2 years OS rates were 95.2%and 93.5%,and the 2 years PFS rates were 90.3%and 87.8%.Subgroup analysis revealed no difference in OS between the 20 mg dexamethasone group and the<20 mg dexamethasone group,but PFS was significantly greater in the 20 mg dexamethasone group(93.9%vs 56.4%,P=0.001).CONCLUSION Dexamethasone or antihistamines can be used before nIC in locally advanced ESCC without affecting short-or long-term efficacy.Administering 20 mg dexamethasone before nIC may improve PFS in ESCC.展开更多
BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary...BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary sites between lncRNA SRA1,miRNA-363-5p,and phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.AIM To investigate the molecular events of SRA1 in the malignant behavior in ESCC.METHODS Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired.SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction.Cell counting Kit-8 assay,transwell invasion assay,glycolysis assay,and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1.The t-test and theχ2 test were used for comparison between groups.Survival curve analysis was performed using the Kaplan-Meier method.RESULTS SRA1 downregulation was identified in ESCC.ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression.The introduction of SRA1 inhibited cell proliferation,glucose uptake,and lactate production in ESCC.In vivo,the growth of ESCC was hindered by SRA1 overexpression.Then,SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p.Lastly,the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.CONCLUSION SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis.The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.展开更多
BACKGROUND The intrapapillary capillary loop(IPCL)characteristics,visualized using magnifying endoscopy,are commonly assessed for preoperative evaluation of the infiltration depth of esophageal squamous cell carcinoma...BACKGROUND The intrapapillary capillary loop(IPCL)characteristics,visualized using magnifying endoscopy,are commonly assessed for preoperative evaluation of the infiltration depth of esophageal squamous cell carcinoma(ESCC).Japan Esophageal Society(JES)classification is the most widely used classification.Microvascular structural changes are evaluated by magnifying endoscopy for the presence or absence of each morphological factor:tortuosity,dilatation,irregular caliber,and different shapes.However,the pathological characteristics of IPCLs have not been thoroughly investigated,especially the microvascular structures corresponding to the deepest parts of the lesions'infiltration.AIM To investigate differences in pathological microvascular structures of ESCC,which correspond to the deepest parts of the lesions'infiltration.METHODS Patients with ESCC and precancerous lesions diagnosed at Peking University Third Hospital were enrolled between January 2019 and April 2023.Patients first underwent magnified endoscopic examination,followed by endoscopic submucosal dissection or surgical treatment.Pathological images were scanned using a threedimensional slice scanner,and the pathological structural differences in different types,according to the JES classification,were analyzed using nonparametric tests and t-tests.RESULTS The 35 lesions were divided into four groups according to the JES classification:A,B1,B2,and B3.Statistical analyses revealed significant differences(aP<0.05)in the short and long calibers,area,location,and density between types A and B.Notably,there were no significant differences in these parameters between types B1 and B2 and between types B2 and B3(P>0.05).However,significant differences in the short calibers,long calibers,and area of IPCL were observed between types B1 and B3(aP<0.05);no significant differences were found in the density or location(P>0.05).CONCLUSION Pathological structures of IPCLs in the deepest infiltrating regions differ among various IPCL types classified by the JES classification under magnifying endoscopy,especially between the types A and B.展开更多
BACKGROUND Multiple primary carcinomas(MPCs)are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual.Synchronous MPCs are rarer than solitary cancers or m...BACKGROUND Multiple primary carcinomas(MPCs)are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual.Synchronous MPCs are rarer than solitary cancers or metachronous MPCs.Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases.CASE SUMMARY A 64-year-old patient presented with dysphagia,without obvious cause.A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results.After multi-disciplinary consultations,combination chemotherapy(a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14)and esophageal cancer radiotherapy were initiated.Based on the results of genetic testing,we switched to a regimen of leucovorin+fluorouracil+oxaliplatin and cetuximab regimen for 8 cycles.Subsequently,capecitabine and bevacizumab were administered until the most recent follow-up,at which the tumor remained stable.CONCLUSION Successful cetuximab chemotherapy treatment provides a reference for the nonoperative and homogeneous treatment of different pathological types of synchronous MCPs.展开更多
Esophageal squamous cell carcinoma(ESCC)is a substantial global health burden.Immune escape mechanisms are important in ESCC progression,enabling cancer cells to escape the surveillance of the host immune system.One k...Esophageal squamous cell carcinoma(ESCC)is a substantial global health burden.Immune escape mechanisms are important in ESCC progression,enabling cancer cells to escape the surveillance of the host immune system.One key player in this process is the Aryl Hydrocarbon Receptor(AhR),which influences multiple cellular processes,including proliferation,differentiation,metabolism,and immune regulation.Dysregulated AhR signaling participates in ESCC development by stimulating carcinogenesis,epithelial-mesenchymal transition,and immune escape.Targeting AhR signaling is a potential therapeutic approach for ESCC,with AhR ligands showing efficacy in preclinical studies.Additionally,modification of AhR ligands and combination therapies present new opportunities for therapeutic intervention.This review aims to address the knowledge gap related to the role of AhR signaling in ESCC pathogenesis and immune escape.展开更多
This editorial discusses the insightful minireview by Rahmati et al.The minireview delves into the role of the aryl hydrocarbon receptor in the development and progression of esophageal squamous cell carcinoma,highlig...This editorial discusses the insightful minireview by Rahmati et al.The minireview delves into the role of the aryl hydrocarbon receptor in the development and progression of esophageal squamous cell carcinoma,highlighting its potential as a promising therapeutic target.The authors concisely summarize the current understanding of how aryl hydrocarbon receptor modula-tion influences immune responses and the tumor microenvironment,offering fresh perspectives on therapeutic strategies.This editorial aimed to emphasize the significance of these findings and their potential impact on future research and clinical practices for the management of esophageal squamous cell carcinoma.展开更多
Objective:To explore and analyze the expression and clinical significance of vascular endothelial growth factor(VEGF),hypoxia-inducible factor 1α(HIF-1α),and metabolic indicators in esophageal squamous cell carcinom...Objective:To explore and analyze the expression and clinical significance of vascular endothelial growth factor(VEGF),hypoxia-inducible factor 1α(HIF-1α),and metabolic indicators in esophageal squamous cell carcinoma(ESCC).Methods:Sixty ESCC patients admitted to the hospital from October 2021 to October 2023 were selected as the ESCC group.Sixty normal healthy patients from the same period were chosen as the control group.Their serum samples and tissue samples were collected.Metabolic indicators of all study subjects were obtained based on the basic biochemical results upon admission.RT-PCR was utilized to detect the expression of VEGF and HIF-1αin ESCC tissues.Results:The expression of VEGF and HIF-1αin the ESCC T3+T4 group was significantly higher than that of the carcinoma in situ(Tis)group,T1+T2 group,and control group.Furthermore,the expression of HIF-1αwas found to be related to the expression of VEGF,showing a significant correlation between the quantities.Significant differences in the levels of metabolic indicators were observed between the ESCC group and the control group(P<0.05).Conclusion:Metabolic indicators are associated with the onset of ESCC in patients.Abnormal lipid metabolism plays a crucial role in the occurrence and development of tumors.The expression of VEGF and HIF-1αin ESCC tissues significantly correlates with the tumor stage,providing a new reference for the diagnosis and treatment of ESCC.展开更多
Esophageal cancer(EC)ranks among the most prevalent malignant tumors affecting the digestive tract.Esophageal squamous cell carcinoma(ESCC)stands as the prevailing pathological subtype,encompassing approximately 90%of...Esophageal cancer(EC)ranks among the most prevalent malignant tumors affecting the digestive tract.Esophageal squamous cell carcinoma(ESCC)stands as the prevailing pathological subtype,encompassing approximately 90%of all EC patients.In clinical stage II-IVA locally advanced ESCC cases,the primary approach to treatment involves a combination of neoadjuvant therapy and surgical resection.Despite concerted efforts,the long-term outcomes for ESCC patients remain unsatisfactory,with dismal prognoses.However,recent years have witnessed remarkable strides in immunotherapy,particularly in the secondand first-line treatment of advanced or metastatic ESCC,with the development of monoclonal antibodies that inhibit programmed death 1 or programmed death ligand 1 demonstrating encouraging responses and perioperative clinical benefits for various malignancies,including ESCC.This comprehensive review aims to present the current landscape of perioperative immunotherapy for resectable ESCC,focusing specifically on the role of immune checkpoint inhibitors during the perioperative period.Additionally,the review will explore promising biomarkers and offer insights into future prospects.展开更多
BACKGROUND Superficial esophageal squamous cell carcinoma(ESCC)is defined as cancer infiltrating the mucosa and submucosa,regardless of regional lymph node metastasis(LNM).Endoscopic resection of superficial ESCC is s...BACKGROUND Superficial esophageal squamous cell carcinoma(ESCC)is defined as cancer infiltrating the mucosa and submucosa,regardless of regional lymph node metastasis(LNM).Endoscopic resection of superficial ESCC is suitable for lesions that have no or low risk of LNM.Patients with a high risk of LNM always need further treatment after endoscopic resection.Therefore,accurately assessing the risk of LNM is critical for additional treatment options.AIM To analyze risk factors for LNM and develop a nomogram to predict LNM risk in superficial ESCC patients.METHODS Clinical and pathological data of superficial ESCC patients undergoing esophagectomy from January 1,2009 to January 31,2016 were collected.Logistic regression analysis was used to predict LNM risk factors,and a nomogram was developed based on risk factors derived from multivariate logistic regression analysis.The receiver operating characteristic(ROC)curve was used to obtain the accuracy of the nomogram model.RESULTSA total of 4660 patients with esophageal cancer underwent esophagectomy.Of these,474 superficial ESCC patientswere enrolled in the final analysis,with 322 patients in the training set and 142 patients in the validation set.Theprevalence of LNM was 3.29%(5/152)for intramucosal cancer and increased to 26.40%(85/322)for submucosalcancer.Multivariate logistic analysis showed that tumor size,invasive depth,tumor differentiation,infiltrativegrowth pattern,tumor budding,and lymphovascular invasion were significantly correlated with LNM.Anomogram using these six variables showed good discrimination with an area under the ROC curve of 0.789(95%CI:0.737-0.841)in the training set and 0.827(95%CI:0.755-0.899)in the validation set.CONCLUSIONWe developed a useful nomogram model to predict LNM risk for superficial ESCC patients which will facilitateadditional decision-making in treating patients who undergo endoscopic resection.展开更多
Accumulating evidence has indicated that long non-coding RNAs(lncRNAs)play critical roles in the development and progression of cancers,including esophageal squamous cell carcinoma(ESCC).However,the mechanisms of lncR...Accumulating evidence has indicated that long non-coding RNAs(lncRNAs)play critical roles in the development and progression of cancers,including esophageal squamous cell carcinoma(ESCC).However,the mechanisms of lncRNAs in ESCC are still incompletely understood and therapeutic attempts for in vivo targeting cancer-associated lncRNA remain a challenge.By RNA-sequencing analysis,we identified that LLNLR-299G3.1 was a novel ESCC-associated lncRNA.LLNLR-299G3.1 was up-regulated in ESCC tissues and cells and promoted ESCC cell proliferation and invasion.Silencing of LLNLR-299G3.1 with ASO(antisense oligonucleotide)resulted in opposite effects.Mechanistically,LLNLR-299G3.1 bound to cancerassociated RNA binding proteins and regulated the expression of cancer-related genes,including OSM,TNFRSF4,HRH3,and SSTR3.ChIRP-seq(chromatin isolation by RNA purification and sequencing)revealed that these genes contained enriched chromatin binding sites for LLNLR-299G3.1.Rescue experiments confirmed that the effects of LLNLR-299G3.1 on ESCC cell proliferation were dependent on interaction with HRH3 and TNFRSF4.Therapeutically,intravenous delivery of placental chondroitin sulfate A binding peptide-coated nanoparticles containing antisense oligonucleotide(pICSA-BP-ANPs)strongly inhibited ESCC tumor growth and significantly improved animal survival in vivo.Overall,our results suggest that LLNLR-299G3.1 promotes ESCC malignancy through regulating gene-chromatin interactions and targeting ESCC by pICSA-BP-ANPs may be an effective strategy for the treatment of lncRNA-associated ESCC.展开更多
BACKGROUND Lugol chromoendoscopy(LCE)has served as a standard screening technique in high-risk patients with esophageal cancer.Nevertheless,LCE is not suitable for general population screening given its side effects.L...BACKGROUND Lugol chromoendoscopy(LCE)has served as a standard screening technique in high-risk patients with esophageal cancer.Nevertheless,LCE is not suitable for general population screening given its side effects.Linked color imaging(LCI)is a novel image-enhanced endoscopic technique that can distinguish subtle differences in mucosal color.AIM To compare the diagnostic performance of LCI with LCE in detecting esophageal squamous cell cancer and precancerous lesions and to evaluate whether LCE can be replaced by LCI in detecting esophageal neoplastic lesions.METHODS In this prospective study,we enrolled 543 patients who underwent white light imaging(WLI),LCI and LCE successively.We compared the sensitivity and specificity of LCI and LCE in the detection of esophageal neoplastic lesions.Clinicopathological features and color analysis of lesions were assessed.RESULTS In total,43 patients(45 neoplastic lesions)were analyzed.Among them,36 patients(38 neoplastic lesions)were diagnosed with LCI,and 39 patients(41 neoplastic lesions)were diagnosed with LCE.The sensitivity of LCI was similar to that of LCE(83.7%vs 90.7%,P=0.520),whereas the specificity of LCI was greater than that of LCE(92.4%vs 87.0%,P=0.007).The LCI procedure time in the esophageal examination was significantly shorter than that of LCE[42(34,50)s vs 160(130,189)s,P<0.001].The color difference between the lesion and surrounding mucosa in LCI was significantly greater than that observed with WLI.However,the color difference in LCI was similar in different pathological types of esophageal squamous cell cancer.CONCLUSION LCI offers greater specificity than LCE in the detection of esophageal squamous cell cancer and precancerous lesions,and LCI represents a promising screening strategy for general populations.展开更多
BACKGROUND The expression status of serum and glucocorticoid-induced protein kinase 3(SGK3)in superficial esophageal squamous cell neoplasia(ESCN)remains unknown.AIM To evaluate the SGK3 overexpression rate in ESCN an...BACKGROUND The expression status of serum and glucocorticoid-induced protein kinase 3(SGK3)in superficial esophageal squamous cell neoplasia(ESCN)remains unknown.AIM To evaluate the SGK3 overexpression rate in ESCN and its influence on the prognosis and outcomes of patients with endoscopic resection.METHODS A total of 92 patients who had undergone endoscopic resection for ESCN with more than 8 years of follow-up were enrolled.Immunohistochemistry was used to evaluate SGK3 expression.RESULTS SGK3 was overexpressed in 55(59.8%)patients with ESCN.SGK3 overexpression showed a significant correlation with death(P=0.031).Overall survival and disease-free survival rates were higher in the normal SGK3 expression group than in the SGK3 overexpression group(P=0.013 and P=0.004,respectively).Cox regression analysis models demonstrated that SGK3 overexpression was an independent predictor of poor prognosis in ESCN patients(hazard ratio 4.729;95% confidence interval:1.042-21.458).CONCLUSION SGK3 overexpression was detected in the majority of patients with endoscopically resected ESCN and was significantly associated with shortened survival.Thus,it might be a new prognostic factor for ESCN.展开更多
Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is ur...Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ESCC.Here,we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy patients.We found that DMRTA1 was extremely upregulated in the non-pathologic complete response(non-pCR)group.The proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression,which could increase cisplatin sensitivity in ESCC.Additionally,suppression of DMRTA1 could decrease the immune escape of esophageal squamous carcinoma cells.Further mechanistic studies suggest that DMRTA1 can promote its expression by binding to the promoter of SOX2,which plays important roles in the progression and chemoresistance of ESCC in the form of positive feedback.Therefore,DMRTA1 could be a potential target to suppress immune escape and overcome chemoresistance in ESCC.展开更多
基金Supported by Xi’an Municipal Health Commission of China,No.2022qn07 and No.2023ms11.
文摘As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major histological subtype of EC,and its incidence and mortality rates are decreasing globally.Due to the lack of specific early symptoms,ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis,and the incidence and mortality rates are still high in many countries,especially in China.Therefore,enormous challenges still exist in the management of ESCC,and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC.Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated,certain promising biomarkers are being investigated to facilitate clinical decision-making.With the advent and advancement of highthroughput technologies,such as genomics,proteomics and metabolomics,valuable biomarkers with high sensitivity,specificity and stability could be identified for ESCC.Herein,we aimed to determine the epidemiological features of ESCC in different regions of the world,especially in China,and focused on novel molecular biomarkers associated with ESCC screening,early diagnosis and prognosis prediction.
基金Supported by Tianjin Key Medical Discipline(Specialty)Construction Project,No.TJYXZDXK-009ATianjin Medical University Cancer Hospital National Natural Science Foundation Cultivation Program,No.220108+3 种基金National Natural Science Foundation of China,No.82373134Science and Technology Development Fund of Tianjin Education Commission for Higher Education,No.2022KJ228Chinese Anti-Cancer Association-Heng Rui Anti-angiogenesis Targeted Tumor Research Fund,No.2021001045and Scientific Research Translational Foundation of Wenzhou Safety(Emergency)Institute of Tianjin University,No.TJUWYY2022025.
文摘BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.
文摘In this editorial,we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023.We focused on identifying risk factors for lymph node metastasis(LNM)in superficial esophageal squamous cell carcinoma(SESCC)patients and how to construct a simple and reliable clinical prediction model to assess the risk of LNM in SESCC patients,thereby helping to guide the selection of an appropriate treatment plan.The current standard treatment for SESCC is radical esophagectomy with lymph node dissection.However,esophagectomy is associated with considerable morbidity and mortality.Endoscopic resection(ER)offers a safer and less invasive alternative to surgical resection and can enable the patient's quality of life to be maintained while providing a satisfactory outcome.However,since ER is a localized treatment that does not allow for lymph node dissection,the risk of LNM in SESCC limits the effectiveness of ER.Understanding LNM status can aid in determining whether patients with SESCC can be cured by ER without the need for additional esophagectomy.Previous studies have shown that tumor size,macroscopic type of tumor,degree of differentiation,depth of tumor invasion,and lymphovascular invasion are factors associated with LNM in patients with SESCC.In addition,tumor budding is commonly associated with LNM,recurrence,and distant metastasis,but this topic has been less covered in previous studies.By comprehensively evaluating the above risk factors for LNM,useful evidence can be obtained for doctors to select appropriate treatments for SESCC patients.
基金supported by the National Natural Science Foundation of China(No.81972681,82103677)Tianjin Education Commission Research Plan Project(No.2021KJ201)+1 种基金Shenzhen High-level Hospital Construction Fund(No.G2022139)Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-009A).
文摘Objective:CD8+T cells are the key effector cells in the anti-tumor immune response.The mechanism underlying the infiltration of CD8+T cells in esophageal squamous cell carcinoma(ESCC)has not been clearly elucidated.Methods:Fresh ESCC tissues were collected and grouped according to the infiltration density of CD8+T cells.After the transcriptome sequencing on these samples and the combined analyses with The Cancer Genome Atlas(TCGA)ESCC data,a secreted protein DEFB1 was selected to explore its potential role in the infiltration of CD8+T cells.Bioinformatics analyses,histological verification and in vitro experiments were then performed.Results:DEFB1 was highly expressed in ESCC,and the high expression of DEFB1 was an independent risk factor for overall survival.Since the up-regulation or down-regulation of DEFB1 did not affect the proliferation,migration and apoptosis of ESCC cells,we speculated that the oncogenic effect of DEFB1 was achieved by regulating microenvironmental characteristics.Bioinformatics analyses suggested that DEFB1 might play a major role in the inflammatory response and anti-tumor immune response,and correlate to the infiltration of immature dendritic cell(imDC)in ESCC.Histological analyses further confirmed that there were less CD8+T cells infiltrated,less CD83+mature DC(mDC)infiltrated and more CD1a+imDC infiltrated in those ESCC samples with high expression of DEFB1.After the treatment with recombinant DEFB1 protein,the maturation of DC was hindered significantly,followed by the impairment of the killing effects of T cells in both 2D and 3D culture in vitro.Conclusions:Tumor-derived DEFB1 can inhibit the maturation of DC and weaken the function of CD8+T cells,accounting for the immune tolerance in ESCC.The role of DEFB1 in ESCC deserves further exploration.
文摘In recent years,endoscopic resection,particularly endoscopic submucosal dis-section,has become increasingly popular in treating non-metastatic superficial esophageal squamous cell carcinoma(ESCC).In this evolving paradigm,it is crucial to identify factors that predict higher rates of lymphatic invasion and poorer outcomes.Larger tumor size,deeper invasion,poorer differentiation,more infiltrative growth patterns(INF-c),higher-grade tumor budding,positive lymphovascular invasion,and certain biomarkers have been associated with lymph node metastasis and increased morbidity through retrospective reviews,leading to the construction of comprehensive nomograms for outcome prediction.If validated by future prospective studies,these nomograms would prove highly applicable in guiding the selection of treatment for superficial ESCC.
基金Supported by Foundation of Henan Educational Committee,No.22A310024and Natural Science Foundation for Young Teachers'Basic Research of Zhengzhou University,No.JC202035025。
文摘Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths globally.The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered,coupled with higher risk of metastasis,which is an exceedingly malignant charac-teristic of cancer,frequently leading to a high mortality rate.Unfortunately,there is currently no specific and effective marker to predict and treat metastasis in ESCC.MicroRNAs(miRNAs)are a class of small non-coding RNA molecules,approximately 22 nucleotides in length.miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence,progression,and prognosis of cancer.Here,we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis,and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors.This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis,with the ultimate aim of reducing the mortality rate among patients with ESCC.
文摘Esophageal squamous cell carcinoma(ESCC)is the most common histological type of esophageal cancer with a poor prognosis.Early diagnosis and prognosis assessment are crucial for improving the survival rate of ESCC patients.With the advancement of artificial intelligence(AI)technology and the proliferation of medical digital information,AI has demonstrated promising sensitivity and accuracy in assisting precise detection,treatment decision-making,and prognosis assessment of ESCC.It has become a unique opportunity to enhance comprehen-sive clinical management of ESCC in the era of precision oncology.This review examines how AI is applied to the diagnosis,treatment,and prognosis assessment of ESCC in the era of precision oncology,and analyzes the challenges and potential opportunities that AI faces in clinical translation.Through insights into future prospects,it is hoped that this review will contribute to the real-world application of AI in future clinical settings,ultimately alleviating the disease burden caused by ESCC.
文摘BACKGROUND Immunochemotherapy involving the combination of programmed cell death 1/programmed cell death ligand 1 inhibitors with chemotherapy has advanced the treatment of locally advanced esophageal squamous cell carcinoma(ESCC).The use of corticosteroids as pretreatment might reduce immunotherapy efficacy.AIM To investigate the impact of baseline corticosteroid use on neoadjuvant immunochemotherapy(nIC)outcomes in locally advanced ESCC patients.METHODS Patients with locally advanced ESCC who received nIC at Sun Yat-sen University Cancer Center and the Third Affiliated Hospital of Sun Yat-sen University were included.Patients were divided into dexamethasone and antihistamine groups on the basis of the administered pretreatment.Antiallergic efficacy and safety were evaluated,as well as its impact on short-term efficacy[complete pathological response(pCR),major pathological response(MPR)]and long-term efficacy[overall survival(OS),progression-free survival(PFS)]of nIC.RESULTS From September 2019 to September 2023,142 patients were analyzed.No severe treatment-related adverse events or deaths were observed.Allergy occurrence was greater in the antihistamine group(P=0.014).Short-term efficacy was not significantly different:The pCR rates were 29.9%and 40.0%,and the MPR rates were 57.9%and 65.7%in the dexamethasone and antihistamine groups,respectively.The long-term efficacy was not significantly different:The 2 years OS rates were 95.2%and 93.5%,and the 2 years PFS rates were 90.3%and 87.8%.Subgroup analysis revealed no difference in OS between the 20 mg dexamethasone group and the<20 mg dexamethasone group,but PFS was significantly greater in the 20 mg dexamethasone group(93.9%vs 56.4%,P=0.001).CONCLUSION Dexamethasone or antihistamines can be used before nIC in locally advanced ESCC without affecting short-or long-term efficacy.Administering 20 mg dexamethasone before nIC may improve PFS in ESCC.
基金Supported by Innovative Team of Jiangsu Province,No.CXTDA2017042Jiangsu Provincial Medical Youth Talent,No.QNRC2016508In-Hospital Project of Taizhou People's Hospital,No.ZL201930.
文摘BACKGROUND The clinical effects and detailed roles of long non-coding RNA(LncRNA)steroid receptor RNA activator 1(SRA1)in esophageal squamous cell carcinoma(ESCC)remain ambiguous.In the present study,the complementary sites between lncRNA SRA1,miRNA-363-5p,and phospholysine phosphohistidine inorganic pyrophosphate phosphatase(LHPP)predicted via bioinformatics analysis stimulated us to hypothesize that miRNA-363-5p/LHPP axis might be required for SRA1-mediated ESCC progression.AIM To investigate the molecular events of SRA1 in the malignant behavior in ESCC.METHODS Thirty-eight ESCC tissues and paired adjacent normal tissues were acquired.SRA1 expression was detected in ESCC tissues and cell lines using quantitative reverse transcription-polymerase chain reaction.Cell counting Kit-8 assay,transwell invasion assay,glycolysis assay,and xenograft tumor model were performed to address the malignant biological behaviors of ESCC cells after the introduction of SRA1.The t-test and theχ2 test were used for comparison between groups.Survival curve analysis was performed using the Kaplan-Meier method.RESULTS SRA1 downregulation was identified in ESCC.ESCC patients exhibiting a low SRA1 expression faced shorter overall survival than those with a high SRA1 expression.The introduction of SRA1 inhibited cell proliferation,glucose uptake,and lactate production in ESCC.In vivo,the growth of ESCC was hindered by SRA1 overexpression.Then,SRA1 overexpresses the LHPP by inhibiting miRNA-363-5p.Lastly,the introduction of small interfering RNA si-LHPP or miRNA-363-5p mimic could abrogate the inhibition roles triggered by SRA1.CONCLUSION SRA1 inhibits the oncogenicity of ESCC via miRNA-363-5p/LHPP axis.The SRA1/miRNA-363-5p/LHPP pathway may be a therapeutic target for ESCC.
基金Supported by Beijing Science and Technology Development Program(Medical and Pharmaceutical Science Project),No.7232200.
文摘BACKGROUND The intrapapillary capillary loop(IPCL)characteristics,visualized using magnifying endoscopy,are commonly assessed for preoperative evaluation of the infiltration depth of esophageal squamous cell carcinoma(ESCC).Japan Esophageal Society(JES)classification is the most widely used classification.Microvascular structural changes are evaluated by magnifying endoscopy for the presence or absence of each morphological factor:tortuosity,dilatation,irregular caliber,and different shapes.However,the pathological characteristics of IPCLs have not been thoroughly investigated,especially the microvascular structures corresponding to the deepest parts of the lesions'infiltration.AIM To investigate differences in pathological microvascular structures of ESCC,which correspond to the deepest parts of the lesions'infiltration.METHODS Patients with ESCC and precancerous lesions diagnosed at Peking University Third Hospital were enrolled between January 2019 and April 2023.Patients first underwent magnified endoscopic examination,followed by endoscopic submucosal dissection or surgical treatment.Pathological images were scanned using a threedimensional slice scanner,and the pathological structural differences in different types,according to the JES classification,were analyzed using nonparametric tests and t-tests.RESULTS The 35 lesions were divided into four groups according to the JES classification:A,B1,B2,and B3.Statistical analyses revealed significant differences(aP<0.05)in the short and long calibers,area,location,and density between types A and B.Notably,there were no significant differences in these parameters between types B1 and B2 and between types B2 and B3(P>0.05).However,significant differences in the short calibers,long calibers,and area of IPCL were observed between types B1 and B3(aP<0.05);no significant differences were found in the density or location(P>0.05).CONCLUSION Pathological structures of IPCLs in the deepest infiltrating regions differ among various IPCL types classified by the JES classification under magnifying endoscopy,especially between the types A and B.
文摘BACKGROUND Multiple primary carcinomas(MPCs)are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual.Synchronous MPCs are rarer than solitary cancers or metachronous MPCs.Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases.CASE SUMMARY A 64-year-old patient presented with dysphagia,without obvious cause.A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results.After multi-disciplinary consultations,combination chemotherapy(a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14)and esophageal cancer radiotherapy were initiated.Based on the results of genetic testing,we switched to a regimen of leucovorin+fluorouracil+oxaliplatin and cetuximab regimen for 8 cycles.Subsequently,capecitabine and bevacizumab were administered until the most recent follow-up,at which the tumor remained stable.CONCLUSION Successful cetuximab chemotherapy treatment provides a reference for the nonoperative and homogeneous treatment of different pathological types of synchronous MCPs.
文摘Esophageal squamous cell carcinoma(ESCC)is a substantial global health burden.Immune escape mechanisms are important in ESCC progression,enabling cancer cells to escape the surveillance of the host immune system.One key player in this process is the Aryl Hydrocarbon Receptor(AhR),which influences multiple cellular processes,including proliferation,differentiation,metabolism,and immune regulation.Dysregulated AhR signaling participates in ESCC development by stimulating carcinogenesis,epithelial-mesenchymal transition,and immune escape.Targeting AhR signaling is a potential therapeutic approach for ESCC,with AhR ligands showing efficacy in preclinical studies.Additionally,modification of AhR ligands and combination therapies present new opportunities for therapeutic intervention.This review aims to address the knowledge gap related to the role of AhR signaling in ESCC pathogenesis and immune escape.
文摘This editorial discusses the insightful minireview by Rahmati et al.The minireview delves into the role of the aryl hydrocarbon receptor in the development and progression of esophageal squamous cell carcinoma,highlighting its potential as a promising therapeutic target.The authors concisely summarize the current understanding of how aryl hydrocarbon receptor modula-tion influences immune responses and the tumor microenvironment,offering fresh perspectives on therapeutic strategies.This editorial aimed to emphasize the significance of these findings and their potential impact on future research and clinical practices for the management of esophageal squamous cell carcinoma.
文摘Objective:To explore and analyze the expression and clinical significance of vascular endothelial growth factor(VEGF),hypoxia-inducible factor 1α(HIF-1α),and metabolic indicators in esophageal squamous cell carcinoma(ESCC).Methods:Sixty ESCC patients admitted to the hospital from October 2021 to October 2023 were selected as the ESCC group.Sixty normal healthy patients from the same period were chosen as the control group.Their serum samples and tissue samples were collected.Metabolic indicators of all study subjects were obtained based on the basic biochemical results upon admission.RT-PCR was utilized to detect the expression of VEGF and HIF-1αin ESCC tissues.Results:The expression of VEGF and HIF-1αin the ESCC T3+T4 group was significantly higher than that of the carcinoma in situ(Tis)group,T1+T2 group,and control group.Furthermore,the expression of HIF-1αwas found to be related to the expression of VEGF,showing a significant correlation between the quantities.Significant differences in the levels of metabolic indicators were observed between the ESCC group and the control group(P<0.05).Conclusion:Metabolic indicators are associated with the onset of ESCC in patients.Abnormal lipid metabolism plays a crucial role in the occurrence and development of tumors.The expression of VEGF and HIF-1αin ESCC tissues significantly correlates with the tumor stage,providing a new reference for the diagnosis and treatment of ESCC.
文摘Esophageal cancer(EC)ranks among the most prevalent malignant tumors affecting the digestive tract.Esophageal squamous cell carcinoma(ESCC)stands as the prevailing pathological subtype,encompassing approximately 90%of all EC patients.In clinical stage II-IVA locally advanced ESCC cases,the primary approach to treatment involves a combination of neoadjuvant therapy and surgical resection.Despite concerted efforts,the long-term outcomes for ESCC patients remain unsatisfactory,with dismal prognoses.However,recent years have witnessed remarkable strides in immunotherapy,particularly in the secondand first-line treatment of advanced or metastatic ESCC,with the development of monoclonal antibodies that inhibit programmed death 1 or programmed death ligand 1 demonstrating encouraging responses and perioperative clinical benefits for various malignancies,including ESCC.This comprehensive review aims to present the current landscape of perioperative immunotherapy for resectable ESCC,focusing specifically on the role of immune checkpoint inhibitors during the perioperative period.Additionally,the review will explore promising biomarkers and offer insights into future prospects.
基金the National Natural Science Foundation of China,No.82173253the Sichuan Province Science and Technology Support Program,No.2022YFH0003 and No.2023NSFSC1900+1 种基金the Postdoctoral Research Foundation of West China Hospital,No.2021HXBH020and the Medico-Engineering Cooperation Funds from the University of Electronic Science and Technology of China and West China Hospital of Sichuan University,No.HXDZ22005.
文摘BACKGROUND Superficial esophageal squamous cell carcinoma(ESCC)is defined as cancer infiltrating the mucosa and submucosa,regardless of regional lymph node metastasis(LNM).Endoscopic resection of superficial ESCC is suitable for lesions that have no or low risk of LNM.Patients with a high risk of LNM always need further treatment after endoscopic resection.Therefore,accurately assessing the risk of LNM is critical for additional treatment options.AIM To analyze risk factors for LNM and develop a nomogram to predict LNM risk in superficial ESCC patients.METHODS Clinical and pathological data of superficial ESCC patients undergoing esophagectomy from January 1,2009 to January 31,2016 were collected.Logistic regression analysis was used to predict LNM risk factors,and a nomogram was developed based on risk factors derived from multivariate logistic regression analysis.The receiver operating characteristic(ROC)curve was used to obtain the accuracy of the nomogram model.RESULTSA total of 4660 patients with esophageal cancer underwent esophagectomy.Of these,474 superficial ESCC patientswere enrolled in the final analysis,with 322 patients in the training set and 142 patients in the validation set.Theprevalence of LNM was 3.29%(5/152)for intramucosal cancer and increased to 26.40%(85/322)for submucosalcancer.Multivariate logistic analysis showed that tumor size,invasive depth,tumor differentiation,infiltrativegrowth pattern,tumor budding,and lymphovascular invasion were significantly correlated with LNM.Anomogram using these six variables showed good discrimination with an area under the ROC curve of 0.789(95%CI:0.737-0.841)in the training set and 0.827(95%CI:0.755-0.899)in the validation set.CONCLUSIONWe developed a useful nomogram model to predict LNM risk for superficial ESCC patients which will facilitateadditional decision-making in treating patients who undergo endoscopic resection.
基金This study was approved by the Medical Ethics Committee of Shenzhen University Health Science Center(protocol no.2016001).
文摘Accumulating evidence has indicated that long non-coding RNAs(lncRNAs)play critical roles in the development and progression of cancers,including esophageal squamous cell carcinoma(ESCC).However,the mechanisms of lncRNAs in ESCC are still incompletely understood and therapeutic attempts for in vivo targeting cancer-associated lncRNA remain a challenge.By RNA-sequencing analysis,we identified that LLNLR-299G3.1 was a novel ESCC-associated lncRNA.LLNLR-299G3.1 was up-regulated in ESCC tissues and cells and promoted ESCC cell proliferation and invasion.Silencing of LLNLR-299G3.1 with ASO(antisense oligonucleotide)resulted in opposite effects.Mechanistically,LLNLR-299G3.1 bound to cancerassociated RNA binding proteins and regulated the expression of cancer-related genes,including OSM,TNFRSF4,HRH3,and SSTR3.ChIRP-seq(chromatin isolation by RNA purification and sequencing)revealed that these genes contained enriched chromatin binding sites for LLNLR-299G3.1.Rescue experiments confirmed that the effects of LLNLR-299G3.1 on ESCC cell proliferation were dependent on interaction with HRH3 and TNFRSF4.Therapeutically,intravenous delivery of placental chondroitin sulfate A binding peptide-coated nanoparticles containing antisense oligonucleotide(pICSA-BP-ANPs)strongly inhibited ESCC tumor growth and significantly improved animal survival in vivo.Overall,our results suggest that LLNLR-299G3.1 promotes ESCC malignancy through regulating gene-chromatin interactions and targeting ESCC by pICSA-BP-ANPs may be an effective strategy for the treatment of lncRNA-associated ESCC.
基金Supported by the National Natural Science Foundation of China,No.81270564 and 82100697.
文摘BACKGROUND Lugol chromoendoscopy(LCE)has served as a standard screening technique in high-risk patients with esophageal cancer.Nevertheless,LCE is not suitable for general population screening given its side effects.Linked color imaging(LCI)is a novel image-enhanced endoscopic technique that can distinguish subtle differences in mucosal color.AIM To compare the diagnostic performance of LCI with LCE in detecting esophageal squamous cell cancer and precancerous lesions and to evaluate whether LCE can be replaced by LCI in detecting esophageal neoplastic lesions.METHODS In this prospective study,we enrolled 543 patients who underwent white light imaging(WLI),LCI and LCE successively.We compared the sensitivity and specificity of LCI and LCE in the detection of esophageal neoplastic lesions.Clinicopathological features and color analysis of lesions were assessed.RESULTS In total,43 patients(45 neoplastic lesions)were analyzed.Among them,36 patients(38 neoplastic lesions)were diagnosed with LCI,and 39 patients(41 neoplastic lesions)were diagnosed with LCE.The sensitivity of LCI was similar to that of LCE(83.7%vs 90.7%,P=0.520),whereas the specificity of LCI was greater than that of LCE(92.4%vs 87.0%,P=0.007).The LCI procedure time in the esophageal examination was significantly shorter than that of LCE[42(34,50)s vs 160(130,189)s,P<0.001].The color difference between the lesion and surrounding mucosa in LCI was significantly greater than that observed with WLI.However,the color difference in LCI was similar in different pathological types of esophageal squamous cell cancer.CONCLUSION LCI offers greater specificity than LCE in the detection of esophageal squamous cell cancer and precancerous lesions,and LCI represents a promising screening strategy for general populations.
基金Supported by National Natural Science Foundation of China,No.82070682Beijing Municipal Science and Technology Commission,China,No.Z181100001718177.
文摘BACKGROUND The expression status of serum and glucocorticoid-induced protein kinase 3(SGK3)in superficial esophageal squamous cell neoplasia(ESCN)remains unknown.AIM To evaluate the SGK3 overexpression rate in ESCN and its influence on the prognosis and outcomes of patients with endoscopic resection.METHODS A total of 92 patients who had undergone endoscopic resection for ESCN with more than 8 years of follow-up were enrolled.Immunohistochemistry was used to evaluate SGK3 expression.RESULTS SGK3 was overexpressed in 55(59.8%)patients with ESCN.SGK3 overexpression showed a significant correlation with death(P=0.031).Overall survival and disease-free survival rates were higher in the normal SGK3 expression group than in the SGK3 overexpression group(P=0.013 and P=0.004,respectively).Cox regression analysis models demonstrated that SGK3 overexpression was an independent predictor of poor prognosis in ESCN patients(hazard ratio 4.729;95% confidence interval:1.042-21.458).CONCLUSION SGK3 overexpression was detected in the majority of patients with endoscopically resected ESCN and was significantly associated with shortened survival.Thus,it might be a new prognostic factor for ESCN.
基金funded by the Department of Education of Yunnan Province(No.2021J0244).
文摘Esophageal squamous cell carcinoma(ESCC)is among the most prevalent causes of cancer-related death in patients worldwide.Resistance to immunotherapy and chemotherapy results in worse survival outcomes in ESCC.It is urgent to explore the underlying molecular mechanism of immune evasion and chemoresistance in ESCC.Here,we conducted RNA-sequencing analysis in ten ESCC tissues from cisplatin-based neoadjuvant chemotherapy patients.We found that DMRTA1 was extremely upregulated in the non-pathologic complete response(non-pCR)group.The proliferation rate of esophageal squamous carcinoma cells was markedly decreased after knockdown of DMRTA1 expression,which could increase cisplatin sensitivity in ESCC.Additionally,suppression of DMRTA1 could decrease the immune escape of esophageal squamous carcinoma cells.Further mechanistic studies suggest that DMRTA1 can promote its expression by binding to the promoter of SOX2,which plays important roles in the progression and chemoresistance of ESCC in the form of positive feedback.Therefore,DMRTA1 could be a potential target to suppress immune escape and overcome chemoresistance in ESCC.