Latest insights into the global epidemiological features,screening,early diagnosis and prognosis prediction of esophageal squamous cell carcinoma

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.

Nomograms and prognosis for superficial esophageal squamous cell carcinoma

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.

Role of deubiquitinase JOSD2 in the pathogenesis of esophageal squamous cell carcinoma

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.

MicroRNAs:A novel signature in the metastasis of esophageal squamous cell carcinoma

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.

Risk factors for lymph node metastasis in superficial esophageal squamous cell carcinoma

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.

Microvascular structural changes in esophageal squamous cell carcinoma pathology according to intrapapillary capillary loop types under magnifying endoscopy

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.

Cetuximab combined with chemotherapy for simultaneous esophageal squamous cell carcinoma and colon adenocarcinoma:A case report

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.

Epidemiology and prognostic nomogram for locally advanced gastric signet ring cell carcinoma:A population-based study

BACKGROUND Gastric signet ring cell carcinoma(GSRC)represents a specific subtype of gastric cancer renowned for its contentious epidemiological features,treatment principles,and prognostic factors.AIM To investigate the epidemiology of GSRC and establish an improved model for predicting the prognosis of patients with locally advanced GSRC(LAGSRC)after surgery.METHODS The annual rates of GSRC incidence and mortality,covering the years 1975 to 2019,were extracted from the Surveillance,Epidemiology,and End Results(SEER)database to explore the temporal trends in both disease incidence and mortality rates using Joinpoint software.The clinical data of 3793 postoperative LAGSRC patients were collected from the SEER database for the analysis of survival rates.The Cox regression model was used to explore the independent prognostic factors for overall survival(OS).The risk factors extracted were used to establish a prognostic nomogram.RESULTS The overall incidence of GSRC increased dramatically between 1975 and 1998,followed by a significant downward trend in incidence after 1998.In recent years,there has been a similarly optimistic trend in GSRC mortality rates.The trend in GSRC showed discrepancies based on age and sex.Receiver operating characteristic curves,calibration curves,and decision curve analysis for 1-year,3-year,and 5-year OS demonstrated the high discriminative ability and clinical utility of this nomogram.The area under the curve indicated that the performance of the new model outperformed that of the pathological staging system.CONCLUSION The model we established can aid clinicians in the early prognostication of LAGSRC patients,resulting in improved clinical outcomes by modifying management strategies and patient health care.

VEGF, HIF-1α, and Metabolic Indicators in Esophageal Squamous Cell Carcinoma

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.

Combination therapy with toripalimab and anlotinib in advanced esophageal squamous cell carcinoma:A case report

BACKGROUND Toripalimab and anlotinib have shown good response in esophageal cancer,with high objective response rate and progression free survival.Thus,they have been approved as second-line or above-line therapy for advanced or unresectable esophageal carcinoma.Combination of these two drugs may have synergistic effects,but evidence of which is lacking.CASE SUMMARY Here,we report on a 73-year-old male,newly diagnosed with advanced esophageal squamous cell carcinoma(ESCC),who received a combination of toripalimab and anlotinib.Complete response was achieved after treatment for 3 mo and remission was maintained up to 14 mo.CONCLUSION The combination therapy of toripalimab and anlotinib is a promising treatment for unresectable ESCC and related clinical trials are warranted.

Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy

Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.

Effectiveness and safety of combined nimotuzumab and S-1 chemotherapy with concurrent radiotherapy for locally advanced esophageal cancer in malnourished and elderly patients:A prospective phaseⅡstudy

Objective:Definitive chemoradiotherapy(dCRT)is the standard treatment for unresectable locally advanced esophageal cancer.However,this treatment is associated with substantial toxicity,and most malnourished or elderly patients are unable to complete this therapy.Therefore,there is a need for a more suitable radiotherapy combination regimen for this population.This study was aimed to evaluate the efficacy and safety of a combination regimen comprising chemotherapy with nimotuzumab and S-1 and concurrent radiotherapy for patients with fragile locally advanced esophageal cancer with a high Nutritional Risk Screening 2002(NRS-2002)score.Methods:Eligible patients with unresectable esophageal carcinoma who had an NRS-2002 score of 2 or higher were enrolled.They were treated with S-1 and nimotuzumab with concurrent radiotherapy,followed by surgery or definitive radiotherapy.The primary endpoint was the locoregional control(LRC)rate.Results:A total of 55 patients who met the study criteria were enrolled.After completion of treatment,surgery was performed in 15 patients and radiotherapy was continued in 40 patients.The median follow-up period was 33.3[95%confidence interval(95%CI,31.4−35.1)]months.The LRC rate was 77.2%(95%CI,66.6%−89.4%)at 1 year in the entire population.The overall survival(OS)rate and event-free survival(EFS)rate were 57.5%and 51.5%at 3 years,respectively.Surgery was associated with better LRC[hazard ratio(HR)=0.16;95%CI,0.04−0.70;P=0.015],OS(HR=0.19;95%CI,0.04−0.80;P=0.024),and EFS(HR=0.25;95%CI,0.08−0.75;P=0.013).Most adverse events were of grade 1 or 2,and no severe adverse events occurred.Conclusions:For malnourished or elderly patients with locally advanced esophageal cancer,radiotherapy combined with nimotuzumab and S-1 is effective and has a good safety profile.

Regulation of TMEM100 expression by epigenetic modification,effects on proliferation and invasion of esophageal squamous carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a prevalent malignancy with a high morbidity and mortality rate.TMEM100 has been shown to be suppressor gene in a variety of tumors,but there are no reports on the role of TMEM100 in esophageal cancer(EC).AIM To investigate epigenetic regulation of TMEM100 expression in ESCC and the effect of TMEM100 on ESCC proliferation and invasion.METHODS Firstly,we found the expression of TMEM100 in EC through The Cancer Genome Atlas database.The correlation between TMEM100 gene expression and the survival of patients with EC was further confirmed through Kaplan-Meier analysis.We then added the demethylating agent 5-AZA to ESCC cell lines to explore the regulation of TMEM100 expression by epigenetic modification.To observe the effect of TMEM100 expression on tumor proliferation and invasion by overexpressing TMEM100.Finally,we performed gene set enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes Orthology-Based Annotation System database to look for pathways that might be affected by TMEM100 and verified the effect of TMEM100 expression on the mitogen-activated protein kinases(MAPK)pathway.RESULTS In the present study,by bioinformatic analysis we found that TMEM100 was lowly expressed in EC patients compared to normal subjects.Kaplan-meier survival analysis showed that low expression of TMEM100 was associated with poor prognosis in patients with EC.Then,we found that the demethylating agent 5-AZA resulted in increased expression of TMEM100 in ESCC cells[quantitative real-time PCR(qRT-PCR)and western blotting].Subsequently,we confirmed that overexpression of TMEM100 leads to its increased expression in ESCC cells(qRT-PCR and western blotting).Overexpression of TMEM100 also inhibited proliferation,invasion and migration of ESCC cells(cell counting kit-8 and clone formation assays).Next,by enrichment analysis,we found that the gene set was significantly enriched in the MAPK signaling pathway.The involvement of TMEM100 in the regulation of MAPK signaling pathway in ESCC cell was subsequently verified by western blotting.CONCLUSION TMEM100 is a suppressor gene in ESCC,and its low expression may lead to aberrant activation of the MAPK pathway.Promoter methylation may play a key role in regulating TMEM100 expression.

Principle and progress of radical treatment for locally advanced esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma is one of the most common malignant tumors in the digestive system in China and the world.Most patients are diagnosed as locally advanced or advanced stage.Concurrent chemoradiotherapy is the standard treatment for locally advanced esophageal squamous cell carcinoma.This study intends to summarize the evidence-based medical evidence of the treatment principle of locally advanced esophageal squamous cell carcinoma,the selection of radiotherapy dose,the outline of radiotherapy target and the selection of chemotherapy scheme.As a result,the effect of radiotherapy and chemotherapy is equivalent to that of surgery for the radical treatment of esophageal squamous cell carcinoma.In the era of immunization,it is recommended to use involved field irradiation.Fluorouracil plus cisplatin regimen is the standard chemotherapy regimen.FOLFOX regimen and paclitaxel plus fluorouracil regimen are optional concurrent chemotherapy regimens.The toxic and side effects of different chemotherapy regimens are different,which can be selected according to the actual situation of patients.

Perioperative immunotherapy for esophageal squamous cell carcinoma:Now and future

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.

Risk factors and a predictive nomogram for lymph node metastasis in superficial esophageal squamous cell carcinoma

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.

Targeting LncRNA LLNLR-299G3.1 with antisense oligonucleotide inhibits malignancy of esophageal squamous cell carcinoma cells in vitro and in vivo

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.

The DMRTA1-SOX2 positive feedback loop promotes progression and chemotherapy resistance of esophageal squamous cell carcinoma

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.

Identification of a three-gene prognostic signature for radioresistant esophageal squamous cell carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is causing a high mortality rate due to the lack of efficient early prognosis markers and suitable therapeutic regimens.The prognostic role of genes responsible for the acquisition of radioresistance in ESCC has not been fully elucidated.AIM To establish a prognostic model by studying gene expression patterns pertinent to radioresistance in ESCC patients.METHODS Datasets were obtained from the Gene Expression Omnibus and The Cancer Genome Atlas databases.The edgeR,a Bioconductor package,was used to analyze mRNA expression between different groups.We screened genes specifically responsible for radioresistance to estimate overall survival.Pearson correlation analysis was performed to confirm whether the expression of those genes correlated with each other.Genes contributing to radioresistance and overall survival were assessed by the multivariate Cox regression model through the calculation ofβi and risk score using the following formula:∑^(n)_(i=1)βi×PSI.RESULTS We identified three prognostic mRNAs(cathepsin S[CTSS],cluster of differentiation 180[CD180],and SLP adapter and CSK-interacting membrane protein[SCIMP])indicative of radioresistance.The expression of the three identified mRNAs was related to each other(r>0.70 and P<0.05).As to 1-year and 3-year overall survival prediction,the area under the time-dependent receiver operating characteristic curve of the signature consisting of the three mRNAs was 0.716 and 0.841,respectively.When stratifying patients based on the risk score derived from the signature,the high-risk group exhibited a higher death risk and shorter survival time than the low-risk group(P<0.0001).Overall survival of the low-risk patients was significantly better than that of the highrisk patients(P=0.018).CONCLUSION We have developed a novel three-gene prognostic signature consisting of CTSS,CD180,and SCIMO for ESCC,which may facilitate the prediction of early prognosis of this malignancy.

Skeletal muscle mass and quality before preoperative chemotherapy influence postoperative long-term outcomes in esophageal squamous cell carcinoma patients

BACKGROUND Previous reports have focused on muscle mass as a prognostic factor in esophageal cancer.AIM To investigate how preoperative body type influences the prognosis of patients with esophageal squamous cell carcinoma who underwent neoadjuvant chemotherapy(NAC)and surgery.METHODS The subjects were 131 patients with clinical stage Ⅱ/Ⅲ esophageal squamous cell carcinoma who underwent subtotal esophagectomy after NAC.Skeletal muscle mass and quality were calculated based on computed tomography images prior to NAC,and their statistical association with long-term outcomes was examined retrospectively in this case-control study.RESULTS The disease-free survival rates in the low psoas muscle mass index(PMI)group vs the high PMI group were 41.3%vs 58.8%(P=0.036),respectively.In the high intramuscular adipose tissue content(IMAC)group vs the low IMAC group,the disease-free survival rates were 28.5%vs 57.6%(P=0.021),respectively.The overall survival(OS)rates for the low PMI group vs the high PMI group were 41.3%vs 64.5%(P=0.008),respectively,and for the high IMAC group vs the low IMAC group,they were 29.9%vs 61.9%(P=0.024),respectively.Analysis of the OS rate revealed significant differences in patients aged 60 years or older(P=0.018),those with pT3 or above disease(P=0.021),or those with lymph node metastasis(P=0.006),aside from PMI and IMAC.Multivariate analysis demonstrated that pT3 or above hazard ratio(HR):1.966,95%confidence interval(CI):1.089-3.550,(P=0.025),lymph node metastasis(HR:2.154,95%CI:1.118-4.148,P=0.022),low PMI(HR:2.266,95%CI:1.282-4.006,P=0.005),and high IMAC(HR:2.089,95%CI:1.036-4.214,P=0.022)were significant prognostic factors for esophageal squamous cell carcinoma.CONCLUSIONSkeletal muscle mass and quality before NAC in patients with esophageal squamous cellcarcinoma are significant prognostic factors for postoperative OS.