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.

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.

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.

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.

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.

Rare esophageal carcinoma-primary adenoid cystic carcinoma of the esophagus: A case report

BACKGROUND Esophageal adenoid cystic carcinoma(EACC)is an exceedingly rare malignant tumor of the esophagus,posing significant challenges in the clinic.CASE SUMMARY This report detailed the case of a 72-year-old male whose diagnosis of EACC was confirmed through postoperative histopathological examination.The patient underwent thoracoscopy-assisted radical resection of the esophageal tumor,coupled with lymph node dissection.Pathological findings revealed an adenoid cystic carcinoma infiltrating the entire layer of the muscularis propria,locally extending into the outer membrane of the esophageal fiber,involving the cardia and exhibiting no lymph node metastasis.The patient’s condition was classified as primary EACC,T3N0M0,per the American Joint Committee on Cancer(2017;8th edition).One month after surgery,the patient received postoperative adjuvant radiation therapy.CONCLUSION In addressing the rarity and high potential for biopsy misdiagnosis of EACC,this study delved into its diagnostic methods and treatment.

Novel milestones for early esophageal carcinoma:From bench to bed

Esophageal cancer(EC)is the seventh most common cancer worldwide,and esophageal squamous cell carcinoma(ESCC)accounts for the majority of cases of EC.To effectively diagnose and treat ESCC and improve patient prognosis,timely diagnosis in the initial phase of the illness is necessary.This article offers a detailed summary of the latest advancements and emerging technologies in the timely identification of ECs.Molecular biology and epigenetics approaches involve the use of molecular mechanisms combined with fluorescence quanti-tative polymerase chain reaction(qPCR),high-throughput sequencing technology(next-generation sequencing),and digital PCR technology to study endogenous or exogenous biomolecular changes in the human body and provide a decision-making basis for the diagnosis,treatment,and prognosis of diseases.The invest-igation of the microbiome is a swiftly progressing area in human cancer research,and microorganisms with complex functions are potential components of the tumor microenvironment.The intratumoral microbiota was also found to be connected to tumor progression.The application of endoscopy as a crucial technique for the early identification of ESCC has been essential,and with ongoing advancements in technology,endoscopy has continuously improved.With the advancement of artificial intelligence(AI)technology,the utilization of AI in the detection of gastrointestinal tumors has become increasingly prevalent.The implementation of AI can effectively resolve the discrepancies among observers,improve the detection rate,assist in predicting the depth of invasion and differentiation status,guide the pericancerous margins,and aid in a more accurate diagnosis of ESCC.

Comparative efficacy and safety between endoscopic submucosal dissection,surgery and definitive chemoradiotherapy in patients with cT1N0M0 esophageal cancer

BACKGROUND Endoscopic submucosal dissection(ESD)and surgical resection are the standard of care for cT1N0M0 esophageal cancer(EC),whereas definitive chemoradiotherapy(d-CRT)is a treatment option.Nevertheless,the comparative efficiency and safety of ESD,surgery and d-CRT for cT1N0M0 EC remain unclear.AIM To compare the efficiency and safety of ESD,surgery and d-CRT for cT1N0M0 EC.METHODS We retrospectively analyzed the hospitalized data of a total of 472 consecutive patients with cT1N0M0 EC treated at Sun Yat-sen University Cancer center between 2017-2019 and followed up until October 30th,2022.We analyzed demographic,medical recorded,histopathologic characteristics,imaging and endoscopic,and follow-up data.The Kaplan-Meier method and Cox proportional hazards modeling were used to analyze the difference of survival outcome by treatments.Inverse probability of treatment weighting(IPTW)was used to minimize potential confounding factors.RESULTS We retrospectively analyzed patients who underwent ESD(n=99)or surgery(n=220)or d-CRT(n=16)at the Sun Yat-sen University Cancer Center from 2017 to 2019.The median follow-up time for the ESD group,the surgery group,and the d-CRT group was 42.0 mo(95%CI:35.0-60.2),45.0 mo(95%CI:34.0-61.75)and 32.5 mo(95%CI:28.3-40.0),respectively.After adjusting for background factors using IPTW,the highest 3-year overall survival(OS)rate and 3-year recurrence-free survival(RFS)rate were observed in the ESD group(3-year OS:99.7% and 94.7% and 79.1%;and 3-year RFS:98.3%,87.4% and 79.1%,in the ESD,surgical,and d-CRT groups,respectively).There was no difference of severe complications occurring between the three groups(P≥0.05).Multivariate analysis showed that treatment method,histology and depth of infiltration were independently associated with OS and RFS.CONCLUSION For cT1N0M0 EC,ESD had better long-term survival and lower hospitalization costs than those who underwent d-CRT and surgery,with a similar rate of severe complications occurring.

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.

Efficacy of concurrent chemoradiotherapy with thalidomide and S-1 for esophageal carcinoma and its influence on serum tumor markers

BACKGROUND Although the current conventional treatment strategies for esophageal carcinoma(EC)have been proven effective,they are often accompanied by serious adverse events.Therefore,it is still necessary to continue to explore new therapeutic strategies for EC to improve the clinical outcome of patients.AIM To elucidate the clinical efficacy of concurrent chemoradiotherapy(CCRT)with thalidomide(THAL)and S-1(tegafur,gimeracil,and oteracil potassium capsules)in the treatment of EC as well as its influence on serum tumor markers(STMs).METHODS First,62 patients with EC treated at the Zibo 148 Hospital between November 2019 and November 2022 were selected and grouped according to the received treatment.Among these,30 patients undergoing CCRT with cis-platinum and 5-fluorouracil were assigned to the control group(Con),and 32 patients receiving CCRT with THAL and S-1 were assigned to the research group(Res).Second,inter-group comparisons were carried out with respect to curative efficacy,incidence of drug toxicities,STMs[carbohydrate antigen 125(CA125)and macrophage inflammatory protein-3α(MIP-3α)],angiogenesis-related indicators[vascular endothelial growth factor(VEGF);VEGF receptor-1(VEGFR-1);basic fibroblast growth factor(bFGF);angiogenin-2(Ang-2)],and quality of life(QoL)[QoL core 30(QLQ-C30)]after one month of treatment.RESULTS The analysis showed no statistical difference in the overall response rate and disease control rate between the two patient cohorts;however,the incidences of grade I–II myelosuppression and gastrointestinal reactions were significantly lower in the Res than in the Con.Besides,the post-treatment CA125,MIP-3α,VEGF,VEGFR-1,bFGF,and Ang-2 Levels in the Res were markedly lower compared with the pre-treatment levels and the corresponding post-treatment levels in the Con.Furthermore,more evident improvements in QLQ-C30 scores from the dimensions of physical,role,emotional,and social functions were determined in the Res.CONCLUSION The above results demonstrate the effectiveness of THAL+S-1 CCRT for EC,which contributes to mild side effects and significant reduction of CA125,MIP-3α,VEGF,VEGFR-1,bFGF,and Ang-2 Levels,thus inhibiting tumors from malignant progression and enhancing patients’QoL.

Multi-institutional analysis of cervical esophageal carcinoma patients treated with definitive chemoradiotherapy: TROD 01-005 study

The aim of this study was to examine the prognostic factors and treatment outcomes of cervical esophageal carcinoma(CEC)patients who underwent definitive chemoradiotherapy(CRT).The clinical data of 175 biopsyconfirmed CEC patients treated with definitive CRT between April 2005 and September 2021 were retrospectively analyzed.The prognostic factors predicting overall survival(OS),progression-free survival(PFS),and local recurrence-free survival(LRFS)were assessed in uni-and multivariable analyses.The median age of the entire cohort was 56 years(range:26–87 years).All patients received definitive radiotherapy with a median total dose of 60 Gy,and 52%of the patients received cisplatin-based concurrent chemotherapy.The 2-year OS,PFS,and LRFS rates were 58.8%,46.9%,and 52.4%,respectively,with a median follow-up duration of 41.6 months.Patients’performance status,clinical nodal stage,tumor size,and treatment response were significant prognostic factors for OS,PFS,and LRFS in univariate analysis.Non-complete treatment response was an independent predictor for poor OS(HR=4.41,95%CI,2.78–7.00,p<0.001)and PFS(HR=4.28,95%CI,2.79–6.58,p<0.001),whereas poor performance score was a predictor for worse LRFS(HR=1.83,95%CI,1.12–2.98,p=0.02)in multivariable analysis.Fifty-two patients(29.7%)experienced grade II or higher toxicity.In this multicenter study,we demonstrated that definitive CRT is a safe and effective treatment for patients with CEC.Higher radiation doses were found to have no effect on treatment outcomes,but a better response to treatment and a better patient performance status did.

Is Escalated Radiation Dose in Definitive Chemoradiotherapy Better for Inoperable Esophageal Carcinoma? A Meta-Analysis and Systematic Review

Purpose: This study aimed to compare the survival benefits between different total radiation doses in definitive chemoradiotherapy (dCRT) for inoperable esophageal carcinoma (EC) based on modern radiotherapy techniques. Methods: A systematic review was performed by searching the databases of PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science. All studies published prior to November 30, 2022, comparing radiation dose and disease-related outcomes in EC patients. The hazard ratio (HR) and odds ratio (OR) were used to describe the risk of outcomes and toxicities. Results: Seven prospective trials involving 1124EC patients were enrolled for analyses. The results revealed that the effect on overall survival (HR = 0.99, 95% CI = 0.85 - 1.16, P = 0.94), local progression-free survival (HR = 0.83, 95% CI = 0.58 - 1.17, P = 0.29), local regional progression-free survival (HR = 0.94, 95% CI = 0.76 - 1.17, P = 0.61), progression-free survival (HR = 0.90, 95% CI = 0.71 - 1.13, P = 0.35) was similar in the high-dose and standard-dose groups. Additionally, a high radiation dose exhibited a potential disadvantage in respiratory toxicities when compared with a standard dose (4.8% vs 2.2%, OR 2.11, P = 0.06). Conclusions: The efficacy of the HD group (≥60 Gy) and the SD group (approximately 50 Gy) for inoperable local advanced EC was similar. However, the HD group exhibited a high radiation dose exhibited a potential disadvantage in respiratory toxicities when compared with a standard dose. Simultaneously, the final results of several ongoing prospective trials regarding the optimal radiation dose in dCRT are awaited.

A prognosis model for predicting immunotherapy response of esophageal cancer based on oxidative stress-related signatures

Oxidative stress(OS)is intimately associated with tumorigenesis and has been considered a potential therapeutic strategy.However,the OS-associated therapeutic target for esophageal squamous cell carcinoma(ESCC)remains unconfirmed.In our study,gene expression data of ESCC and clinical information from public databases were downloaded.Through LASSO-Cox regression analysis,a risk score(RS)signature map of prognosis was constructed and performed external verification with the GSE53625 cohort.The ESTIMATE,xCell,CIBERSORT,TIMER,and ImmuCellAI algorithms were employed to analyze infiltrating immune cells and generate an immune microenvironment(IM).Afterward,functional enrichment analysis clarified the underlying mechanism of the model.Nomogram was utilized for forecasting the survival rate of individual ESCC cases.As a result,we successfully constructed an OS-related genes(OSRGs)model and found that the survival rate of high-risk groups was lower than that of low-risk groups.The AUC of the ROC verified the strong prediction performance of the signal in these two cohorts further.According to independent prognostic analysis,the RS was identified as an independent risk factor for ESCC.The nomogram and follow-up data revealed that the RS possesses favorable predictive value for the prognosis of ESCC patients.qRT-PCR detection demonstrated increased expression of MPC1,COX6C,CYB5R3,CASP7,and CYCS in esophageal cancer patients.In conclusion,we have constructed an OSRGs model for ESCC to predict patients’prognosis,offering a novel insight into the potential application of the OSRGs model in ESCC.

Transcriptome sequencing reveals novel biomarkers and immune cell infiltration in esophageal tumorigenesis

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most common malignancies worldwide,and its development comprises a multistep process from intraepithelial neoplasia(IN)to carcinoma(CA).However,the critical regulators and underlying molecular mechanisms remain largely unknown.AIM To explore the genes and infiltrating immune cells in the microenvironment that are associated with the multistage progression of ESCC to facilitate diagnosis and early intervention.METHODS A mouse model mimicking the multistage development of ESCC was established by providing warter containing 4-nitroquinoline 1-oxide(4NQO)to C57BL/6 mice.Moreover,we established a control group without 4NQO treatment of mice.Then,transcriptome sequencing was performed for esophageal tissues from patients with different pathological statuses,including low-grade IN(LGIN),high-grade IN(HGIN),and CA,and controlled normal tissue(NOR)samples.Differentially expressed genes(DEGs)were identified in the LGIN,HGIN,and CA groups,and the biological functions of the DEGs were analyzed via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses.The CIBERSORT algorithm was used to detect the pattern of immune cell infilt-ration.Immunohistochemistry(IHC)was also conducted to validate our results.Finally,the Luminex multiplex cytokine analysis was utilized to measure the serum cytokine levels in the mice.RESULTS Compared with those in the NOR group,a total of 681541,and 840 DEGs were obtained in the LGIN,HGIN,and CA groups,respectively.Using the intersection of the three sets of DEGs,we identified 86 genes as key genes involved in the development of ESCC.Enrichment analysis revealed that these genes were enriched mainly in the keratinization,epidermal cell differentiation,and interleukin(IL)-17 signaling pathways.CIBERSORT analysis revealed that,compared with those in the NOR group,M0 and M1 macrophages in the 4NQO group showed stronger infiltration,which was validated by IHC.Serum cytokine analysis revealed that,compared with those in the NOR group,IL-1βand IL-6 were upregulated,while IL-10 was downregulated in the LGIN,HGIN,and CA groups.Moreover,the expression of the representative key genes,such as S100a8 and Krt6b,was verified in external human samples,and the results of immunohistochemical staining were consistent with the findings in mice.CONCLUSION We identified a set of key genes represented by S100a8 and Krt6b and investigated their potential biological functions.In addition,we found that macrophage infiltration and abnormal alterations in the levels of inflam-mation-associated cytokines,such as IL-1β,IL-6,and IL-10,in the peripheral blood may be closely associated with the development of ESCC.

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.

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.

Mucosal esophageal carcinoma following endoscopic submucosal dissection with giant gastric metastasis:A case report and review of literature

BACKGROUND Esophageal carcinoma is a highly aggressive digestive cancer responsible for a notable proportion of cancer-related deaths worldwide.Its elevated metastatic rate contributes to a poor prognosis in affected patients.In this case review,we aim to summarize the metastatic characteristics of intramural gastric metastasis(IGM)in mucosal esophageal squamous carcinoma.CASE SUMMARY A 56-year-old man was admitted to our hospital because of a dry cough with an esophageal sensation for one year.Endoscopic examination revealed a 2.0 cm 1.0 cm,superficial esophageal squamous cell carcinoma,and the patient underwent endoscopic submucosal dissection(ESD).Fifteen months after ESD,positron emission tomography/computed tomography revealed that the metabolism of the stomach cardia wall had increased slightly.However,the mucosa of the gastric cardia was smooth under gastroendoscopy.Two years after ESD,endoscopic examination revealed a giant gastric cardia carcinoma,while the esophageal mucosa was smooth,and no advanced cancer was found.A biopsy of the gastric cardia indicated squamous-cell carcinoma.The patient received immunochemotherapy and radiotherapy for esophageal cancer for 8 mo and is currently under follow-up.CONCLUSION Early-stage esophageal carcinoma with IGM is rare.Despite the ESD of the primary lesion,IGM may still occur and should be closely monitored after ESD.

Preliminary Exploration of the Clinical Features and Immunological Correlation between TIGIT and Esophageal Squamous Cell Carcinoma

Objective: To analyze the relationship between TIGIT and clinical features of Esophageal Squamous Cell Carcinoma, we use transcriptomic data from the TCGA database, and to investigate the relationship between TIGIT and the immune microenvironment of Esophageal Squamous Cell Carcinoma, to provide a basis for improving the treatment strategy and prognosis of patients with Esophageal Squamous Cell Carcinoma. Methods: RNA sequencing data and clinical data corresponding to cancer tissues were obtained from the TCGA database for Esophageal carcinoma, Esophageal Squamous Cell Carcinoma tissues, and paraneoplastic tissues;then we analyzed the differences in TIGIT expression in Esophageal carcinoma, Esophageal Squamous Cell Carcinoma, and normal esophageal tissues;then we analyzed the relationship between TIGIT expression levels and overall survival in Esophageal Squamous Cell Carcinoma;finally, we explored the relationship between TIGIT expression levels and overall survival in Esophageal Squamous Cell Carcinoma. We investigated the relationship between TIGIT and the tumor immune microenvironment of Esophageal Squamous Cell Carcinoma by tumor immune infiltration and functional enrichment analysis. Results: Our study revealed that TIGIT was highly expressed in Esophageal Squamous Cell Carcinoma, and patients with high TIGIT expression had worse overall survival. We also found a close relationship between TIGIT expression levels and the immune microenvironment of Esophageal Squamous Cell Carcinoma, with high TIGIT expression positively correlated with multiple immune cells. Conclusion: Our study demonstrates that TIGIT is associated with Esophageal Squamous Cell Carcinoma malignancy and is closely linked to the immune microenvironment. Furthermore, high expression of TIGIT often predicts poorer clinical features.

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.

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.