Is Helicobacter pylori infection protective against esophageal cancer?

Helicobacter pylori(H.pylori)infection affects a substantial proportion of the global population and causes various gastric disorders,including gastric cancer.Recent studies have found an inverse relationship between H.pylori infection and eso-phageal cancer(EC),suggesting a protective role against EC.This editorial focuses on the possible mechanisms underlying the role of H.pylori infection in EC and explores the role of gut microbiota in esophageal carcinogenesis and the prac-ticality of H.pylori eradication.EC has two major subtypes:Esophageal squamous cell carcinoma(ESCC)and esophageal adenocarcinoma(EAC),which have different etiologies and risk factors.Gut microbiota can contribute to EC via inflammation-induced carcinogenesis,immunomodulation,lactagenesis,and genotoxin production.H.pylori infection is said to be inversely related to EAC,protecting against EAC by inducing atrophic gastritis,altering serum ghrelin levels,and triggering cancer cell apoptosis.Though H.pylori infection has no significant association with ESCC,COX-2-1195 polymorphisms and endogenous nitrosamine production can impact the risk of ESCC in H.pylori-infected in-dividuals.There are concerns regarding a plausible increase in EC after H.pylori eradication treatments.However,H.pylori eradication is not associated with an increased risk of EC,making it safe from an EC perspective.

Artificial intelligence-assisted esophageal cancer management:Now and future

Esophageal cancer poses diagnostic,therapeutic and economic burdens in highrisk regions.Artificial intelligence(AI)has been developed for diagnosis and outcome prediction using various features,including clinicopathologic,radiologic,and genetic variables,which can achieve inspiring results.One of the most recent tasks of AI is to use state-of-the-art deep learning technique to detect both early esophageal squamous cell carcinoma and esophageal adenocarcinoma in Barrett’s esophagus.In this review,we aim to provide a comprehensive overview of the ways in which AI may help physicians diagnose advanced cancer and make clinical decisions based on predicted outcomes,and combine the endoscopic images to detect precancerous lesions or early cancer.Pertinent studies conducted in recent two years have surged in numbers,with large datasets and external validation from multi-centers,and have partly achieved intriguing results of expert’s performance of AI in real time.Improved pre-trained computer-aided diagnosis algorithms in the future studies with larger training and external validation datasets,aiming at real-time video processing,are imperative to produce a diagnostic efficacy similar to or even superior to experienced endoscopists.Meanwhile,supervised randomized controlled trials in real clinical practice are highly essential for a solid conclusion,which meets patient-centered satisfaction.Notably,ethical and legal issues regarding the blackbox nature of computer algorithms should be addressed,for both clinicians and regulators.

Endoscopic management of esophageal cancer

Esophageal cancer(EC)generally consists of squamous cell carcinoma(which arise from squamous epithelium)and adenocarcinoma(which arise from columnar epithelium).Due to the increased recognition of risk factors associated with EC and the development of screening programs,there has been an increase in the diagnosis of early EC.Early EC is amenable to curative therapy by endoscopy,which can be performed by either endoscopic resection or endoscopic ablation.Endoscopic resection consists of either endoscopic mucosal resection(preferred in cases of adenocarcinoma)or endoscopic submucosal dissection(preferred in cases of squamous cell carcinoma).Endoscopic ablation can be performed by either radiofrequency ablation,cryotherapy,argon plasma coagulation or photodynamic therapy,amongst others.Endoscopy can also assist in the management of complications post-esophageal surgery,such as anastomotic leaks and perforations.Finally,there is a growing role for endoscopy to manage end-of-life palliative symptoms,especially dysphagia.The growing use of esophageal stents,debulking therapy and dilation can assist in improving a patient’s quality of life.In this review,we examine the multiple roles of endoscopy in the management of patients with EC.

Four cancer cases after esophageal atresia repair: Time to start screening the upper gastrointestinal tract

Esophageal atresia(EA) is one of the most common congenital digestive malformations and requires surgical correction early in life. Dedicated centers have reported survival rates up to 95%. The most frequent comorbidities after EA repair are dysphagia(72%) and gastroesophageal reflux(GER)(67%). Chronic GER after EA repair might lead to mucosal damage, esophageal stricturing, Barrett's esophagus and eventually esophageal adenocarcinoma. Several long-term follow-up studies found an increased risk of Barrett's esophagus and esophageal carcinoma in EA patients, both at a relatively young age. Given these findings, the recent ESPGHAN-NASPGHAN guideline recommends routine endoscopy in adults born with EA. We report a series of four EA patients who developed a carcinoma of the gastrointestinal tract: three esophageal carcinoma and one colorectal carcinoma in a colonic interposition. These cases emphasize the importance of lifelong screening of the upper gastrointestinal tract in EA patients.

Reduced esophageal cancer incidence in statin users,particularly with cyclo-oxygenase inhibition

AIM:To examine the association between statin use and the development of esophageal cancer METHODS:We performed a systematic review and meta-analysis.Multiple databases(Pubmed,EMBASE,Cochrane Library,Web of Science,Wiley Interscience and Google Scholar) were systematically searched for studies reporting the association of statin use and the development of esophageal cancer.Literature searching and data abstraction were performed independently by two separate researchers.The quality of studies reviewed was evaluated using the Newcastle-Ottawa Quality assessment scale.Meta-analysis on the relationship between statin use and cancer incidence was performed.The effect of the combination of statin plus a cyclo-oxygenase inhibitor was also examined.RESULTS:Eleven studies met eligibility criteria,9 high and 2 medium quality.All were observational studies.Studies examining adenocarcinoma development in Barrett's esophagus included 317 cancers and 1999 controls,population-based studies examining all esophageal cancers included 371203 cancers and 6083150 controls.In the Barrett's population the use of statins(OR = 0.57;95%CI:0.43-0.75) and cyclo-oxygenase inhibitors(OR = 0.59;95%CI:0.45-0.77) were independently associated with a reduced incidence of adenocarcinoma.Combined use of a statin plus cyclooxygenase inhibitor was associated with an even lower adenocarcinoma incidence(OR = 0.26;95%CI:0.1-0.68).There was more heterogeneity in the population-based studies but pooled adjusted data showed that statin use was associated with a lower incidence of all combined esophageal cancers(OR = 0.81;95%CI:0.75-0.88).CONCLUSION:Statin use in patients with Barrett's oesophagus is associated with a significantly lower incidence of adenocarcinoma.The chemopreventive actions of statins,especially combined with cyclooxygenase inhibitors deserve further exploration.

Barrett's esophagus with high grade dysplasia is associated with non-esophageal cancer

AIM To study factors associated with esophageal and nonesophageal cancer morbidity among Barrett's esophagus(BE) patients. METHODS A cohort study within a single tertiary center included 386 consecutive patients with biopsy proven BE, who were recruited between 2004-2014. Endoscopic and histologic data were prospectively recorded. Cancer morbidity was obtained from the national cancer registry. Main outcomes were BE related(defined as esophagus and cardia) and non-BE related cancers(all other cancers). Cancer incidence and all-causemortality were compared between patients with highgrade dysplasia(HGD) and with low-grade or no dysplasia(non-HGD) using Kaplan-Meier curves and cox regression models.RESULTS Of the 386 patients, 12 had HGD, 7 had a BE related cancer. There were 75(19.4%) patients with 86 cases of lifetime cancers, 76 of these cases were non-BE cancers. Seven(1.8%) and 18(4.7%) patients had BE and non-BE incident cancers, respectively. Twelve(3.1%) patients had HGD as worst histologic result. Two(16.7%) and 16(4.4%) incident non-BE cancers occurred in the HGD and non-HGD group, respectively. Ten-year any cancer and non-BE cancer free survival was 63% and 82% in the HGD group compared to 93% and 95% at the non-HGD group, respectively. Log-rank test for patients with more than one endoscopy, assuring longer follow up, showed a significant difference(P < 0.001 and P = 0.017 respectively). All-cause mortality was not significantly associated with BE HGD.CONCLUSION Patients with BE and HGD, may have a higher risk for all-cause cancer morbidity. The implications on cancer prevention recommendations should be further studied.

S100A4 in esophageal cancer:Is this the one to blame?

Metastasis is the main reason for cancer-related death.S100A4 is one of the key molecules involved in this event.Several studies have shown that overexpression of S100A4 in non-metastatic cancer cells can make them become metastatic,and knockdown of S100A4 in metastatic cancer cells can curtail their invasive nature.A study by Chen et al published in the World J Gastroenterol 18(9):915-922,2012 is a typical example.This study showed in vitro and in vivo evidence that S100A4 expression level determines the invasiveness of esophageal squamous carcinoma.Considering the fact that more than half of the cancer-related deaths are caused by malignancies derived from the digestive system and esophageal cancer is the 4th top contributor to this fraction,this study warrants more attention.

Glutathione S-transferase M1 polymorphism and esophagealcancer risk:An updated meta-analysis based on 37 studies

AIM: To evaluate the relationship between glutathione S-transferase M1(GSTM1) polymorphism and susceptibility to esophageal cancer(EC).METHODS: A comprehensive search of the United States National Library of Medicine Pub Med database and the Elsevier, Springer, and China National Knowledge Infrastructure databases for all relevant studies was conducted using combinations of the following terms: "glutathione S-transferase M1", "GSTM1", "polymorphism", and "EC"(until November 1, 2014). The statistical analysis was performed using the SAS software(v.9.1.3; SAS Institute, Cary, NC, United States) and the Review Manager software(v.5.0; Oxford, England); crude odds ratios(ORs) with 95% confidence intervals(CIs) were used to assess the association between the GSTM1 null genotype and the risk of EC.RESULTS: A total of 37 studies involving 2236 EC cases and 3243 controls were included in this metaanalysis. We observed that the GSTM1 null genotype was a significant risk factor for EC in most populations(OR = 1.33, 95%CI: 1.12-1.57, P_(heterogeneity) < 0.000001, and I2 = 77.0%), particularly in the Asian population(OR = 1.53, 95%CI: 1.26-1.86, P_(heterogeneity)< 0.000001, and I2 = 77.0%), but not in the Caucasian population(OR = 1.02, 95%CI: 0.87-1.19, P_(heterogeneity) = 0.97, and I2 = 0%).CONCLUSION: The GSTM1 null polymorphism may be associated with an increased risk for EC in Asian but not Caucasian populations.

Artificial intelligence and early esophageal cancer

The development of esophageal cancer(EC)from early to advanced stage results in a high mortality rate and poor prognosis.Advanced EC not only poses a serious threat to the life and health of patients but also places a heavy economic burden on their families and society.Endoscopy is of great value for the diagnosis of EC,especially in the screening of Barrett’s esophagus and early EC.However,at present,endoscopy has a low diagnostic rate for early tumors.In recent years,artificial intelligence(AI)has made remarkable progress in the diagnosis of digestive system tumors,providing a new model for clinicians to diagnose and treat these tumors.In this review,we aim to provide a comprehensive overview of how AI can help doctors diagnose early EC and precancerous lesions and make clinical decisions based on the predicted results.We analyze and summarize the recent research on AI and early EC.We find that based on deep learning(DL)and convolutional neural network methods,the current computer-aided diagnosis system has gradually developed from in vitro image analysis to real-time detection and diagnosis.Based on powerful computing and DL capabilities,the diagnostic accuracy of AI is close to or better than that of endoscopy specialists.We also analyze the shortcomings in the current AI research and corresponding improvement strategies.We believe that the application of AI-assisted endoscopy in the diagnosis of early EC and precancerous lesions will become possible after the further advancement of AI-related research.

Esophageal squamous cell carcinoma-precursor lesions and early diagnosis

Squamous cell carcinoma of the esophagus (SCCE) carries a poor prognosis due to late diagnosis.Early detection is highly desirable,since surgical and endoscopic resection offers the only possible cure for esophageal cancer.Population screening should be undertaken in high risk areas,and in low or moderate risk areas for people with risk factors (alcoholics,smokers,mate drinkers,history of head and neck cancer,achalasia and lye stricture of the esophagus).Esophageal balloon cytology is an easy and inexpensive sampling technique,but the current methods are insufficient for primary screening due to sampling errors.Conventional endoscopy with biopsy remains the standard procedure for the identification of pre-malignant and early malignant changes in esophageal mucosa and endoscopic detection.It may be enhanced by several techniques such as dye and optic chromoendoscopy,magnifying endoscopy,and optical-based spectroscopic and imaging modalities.Since more than 80% of SCCE deaths occur in developing countries,where expensive techniques such as narrow band imaging (NBI) and autofluorescence imaging are unavailable,the most cost-effective tool for targeting biopsies may be Lugol dye chromoendoscopy,since it is easy,accurate,inexpensive and available worldwide.In ideal conditions,or in developed countries,is it reasonable to think that optimal detection will require a combination of techniques,such as the combination of Lugol’s chromoendoscopy and NBI to identify esophageal areas that require further characterization by a high resolution technique.The efficacy and cost-effectiveness will determine whether these modalities will become part of standard endoscopy practice.

Role of microbial dysbiosis in the pathogenesis of esophageal mucosal disease:A paradigm shift from acid to bacteria?

Genomic sequencing,bioinformatics,and initial speciation(e.g.,relative abundance)of the commensal microbiome have revolutionized the way we think about the“human”body in health and disease.The interactions between the gut bacteria and the immune system of the host play a key role in the pathogenesis of gastrointestinal diseases,including those impacting the esophagus.Although relatively stable,there are a number of factors that may disrupt the delicate balance between the luminal esophageal microbiome(EM)and the host.These changes are thought to be a product of age,diet,antibiotic and other medication use,oral hygiene,smoking,and/or expression of antibiotic products(bacteriocins)by other flora.These effects may lead to persistent dysbiosis which in turn increases the risk of local inflammation,systemic inflammation,and ultimately disease progression.Research has suggested that the etiology of gastroesophageal reflux disease-related esophagitis includes a cytokine-mediated inflammatory component and is,therefore,not merely the result of esophageal mucosal exposure to corrosives(i.e.,acid).Emerging evidence also suggests that the EM plays a major role in the pathogenesis of disease by inciting an immunogenic response which ultimately propagates the inflammatory cascade.Here,we discuss the potential role for manipulating the EM as a therapeutic option for treating the root cause of various esophageal disease rather than just providing symptomatic relief(i.e.,acid suppression).

Issues and controversies in esophageal inlet patch

The proximal esophagus is rarely examined,and its inspection is often inadequate.Optical chromoendoscopy techniques such as narrow band imaging improve the detection rate of inlet patches in the proximal esophagus,a region in which their prevalence is likely underestimated.Various studies have reported correlations between these esophageal marks with different issues such as Barrett’s esophagus,but these findings remain controversial.Conflicting reports complicate the process of interpreting the clinical features of esophageal inlet patches and underestimate their importance.Unfortunately,the limited clinical data and statistical analyses make reaching any conclusions difficult.It is hypothesized that inlet patches are correlated with various esophageal and extraesophageal symptoms,diagnoses and the personalized therapeutic management of patients with inlet patches as well as the differential diagnosis for premalignant lesions or early cancers.Due to its potential underdiagnosis,there are no consensus guidelines for the management and follow up of inlet patches.This review focuses on questions that were raised from published literature on esophageal inlet patches in adults.

Update on endoscopic diagnosis, management and surveillance strategies of esophageal diseases

In the last few decades, upper gastrointestinal endoscopy has become the most complementary test for investigation of esophageal diseases. Its accessibility and safety guarantee wide clinical utilization in patients with suspected benign and malignant diseases of the esophagus. Recent technological advances in endoscopic imaging and tissue analysis obtained from the esophagus have been useful to better understand and manage highly relevant diseases such as gastroesophageal reflux disease, eosinophilic esophagitis and esophageal cancer. Using endoscopy to elucidate esophageal disorders in children has been another field of intensive and challenging research. This editorial highlights the latest advances in the endoscopic management of esophageal diseases, and focuses on Barrett’s esophagus, esophageal cancer, eosinophilic esophagitis, as well as esophageal disorders in the pediatric population.

Resection of early esophageal neoplasms: The pendulum swings from surgical to endoscopic management

Esophageal cancer is a highly lethal disease and is the sixth leading cause of cancer related mortality in the world.The standard treatment is esophagectomy which is associated with significant morbidity and mortality.This led to development of minimally invasive,organ sparing endoscopic therapies which have comparable outcomes to esophagectomy in early cancer.These include endoscopic mucosal resection and endoscopic submucosal dissection.In early squamous cell cancer,endoscopic submucosal dissection is preferred as it is associated with cause specific 5-year survival rates of 100%for M1 and M2 tumors and 85%for M3 and SM1 tumors and low recurrence rates.In early adenocarcinoma,endoscopic resection of visible abnormalities is followed by ablation of the remaining flat Barrett’s mucosa to prevent recurrences.Radiofrequency ablation is the most widely used ablation modality with others being cryotherapy and argon plasma coagulation.Focal endoscopic mucosal resection followed by radiofrequency ablation leads to eradication of neoplasia in 93.4%of patients and eradication of intestinal metaplasia in 73.1%of patients.Innovative techniques such as submucosal tunneling with endoscopic resection are developed for management of submucosal tumors of the esophagus.This review includes a discussion of various endoscopic techniques and their clinical outcomes in early squamous cell cancer,adenocarcinoma and submucosal tumors.An overview of comparison between esophagectomy and endoscopic therapy are also presented.

Advances and horizons for artificial intelligence of endoscopic screening and surveillance of gastric and esophageal disease

The development of artificial intelligence in endoscopic assessment of the gastrointestinal tract has shown progressive enhancement in diagnostic acuity.This review discusses the expanding applications for gastric and esophageal diseases.The gastric section covers the utility of AI in detecting and characterizing gastric polyps and further explores prevention,detection,and classification of gastric cancer.The esophageal discussion highlights applications for use in screening and surveillance in Barrett's esophagus and in high-risk conditions for esophageal squamous cell carcinoma.Additionally,these discussions highlight applications for use in assessing eosinophilic esophagitis and future potential in assessing esophageal microbiome changes.

Cryotherapy in the management of premalignant and malignant conditions of the esophagus

Endoscopic cryotherapy is a relatively new thermal ablative modality used for the treatment of neoplastic lesions of the esophagus. It relies on cycles of rapid cooling and thawing to induce tissue destruction with a cryogen(liquid nitrogen or carbon dioxide) leading to intra and extra-cellular damage. Surgical treatment was once considered the standard therapeutic intervention for neoplastic diseases of the esophagus and is associated with considerable rates of morbidity and mortality. Several trials that evaluated cryotherapy in Barrett's esophagus(BE) associated neoplasia showed reasonable efficacy rates and safety profile. Cryotherapy has also found applications in the treatment of esophageal cancer, both for curative and palliative intent. Cryotherapy has also shown promising results as salvage therapy in cases refractory to radiofrequency ablation treatment. Cryoballoon focal ablation using liquid nitrogen is a novel mode of cryogen delivery which has been used for the treatment of BE with dysplasia and squamous cell carcinoma. Most common side effects of cryotherapy reported in the literature include mild chest discomfort, esophageal strictures and bleeding. In conclusion, cryotherapy is an effective and safe method for the treatment of esophageal neoplastic processes, ranging from early stages of low grade dysplasia to esophageal cancer.

Role of chemoprophylaxis with either NSAIDs or statins in patients with Barrett's esophagus

The incidence of esophageal adenocarcinoma,a poor prognosis neoplasia,has risen dramatically in recent decades.Barrett’s esophagus represents the best-known risk factor for esophageal adenocarcinoma development.Non-steroidal anti-inflammatory drugs through cyclooxygenase-2 inhibition and prostaglandin metabolism regulation could control cell proliferation,increase cell apoptosis and regulate the expression of growth and angiogenic factors.Statins can achieve equivalent effects through prenylation and subsequently control of cellular signaling cascades.At present,epidemiological studies are small and underpowered.Their data could not justify either medication as a chemo-preventive agent.Population based studies have shown a 43%reduction of the odds of developing an esophageal adenocarcinoma,leaving out or stating a 25%reduction in patients consuming non-aspirin nonsteroidal antiinflammatory drugs and a 50%reduction in those patients consuming aspirin.They have also stated a 19%reduction of esophageal cancer incidence when statins have been used.Observational studies have shown that non-steroidal anti-inflammatory drugs could reduce theadenocarcinoma incidence in patients with Barrett’s esophagus by 41%,while statins could reduce the risk by 43%.The cancer preventive effect has been enhanced in those patients taking a combination of non-steroidal anti-inflammatory drugs and statins(a 74%decrease).Observational data are equivocal concerning the efficacy of non-steroidal anti-inflammatory drug subclasses.Non-steroidal anti-inflammatory drugs clearly have substantial potential for toxicity,while statins are rather safe drugs.In conclusion,both non-steroidal anti-inflammatory drugs and statins are promising chemopreventive agents and deserve further exploration with interventional studies.In the meanwhile,their use is justified only in patients with cardiovascular disease.

Artificial intelligence for cancer detection in upper gastrointestinal endoscopy, current status, and future aspirations

This minireview discusses the benefits and pitfalls of machine learning,and artificial intelligence in upper gastrointestinal endoscopy for the detection and characterization of neoplasms.We have reviewed the literature for relevant publications on the topic using PubMed,IEEE,Science Direct,and Google Scholar databases.We discussed the phases of machine learning and the importance of advanced imaging techniques in upper gastrointestinal endoscopy and its association with artificial intelligence.

BRD4通过靶向GSTP1调控食管癌TE-1细胞顺铂敏感性

目的揭示食管癌组织中溴结构域蛋白4(BRD4)表达水平,并分析其与谷胱甘肽硫基转移酶P1(GSTP1)分子的联系,探究BRD4在人食管癌细胞(TE-1细胞)顺铂敏感性调控中的作用。方法基于癌症基因组图谱(TCGA)数据利用R语言包解析BRD4在食管癌及癌旁正常组织中表达情况;基因表法普交互分析(GEPIA2)在线评估食管癌肿瘤组织中BRD4与化疗药物解毒酶GSTP1表达的联系;通过小干扰RNA(siRNA)和靶向抑制剂(+)-JQ1(25、50和100 nM)分别处理食管癌TE-1细胞,通过蛋白免疫印迹法(Western blot)验证食管癌TE-1细胞中BRD4及GSTP1蛋白表达变化;TE-1细胞(+)-JQ1预处理(50 nM,24 h)前后及结合顺铂(DDP,5μg/ml,24 h),运用Western blot实验检测凋亡相关蛋白Bcl-2关联X蛋白(Bax)、淋巴细胞瘤-2(Bcl-2)、半胱氨酸天冬氨酸蛋白酶3(Caspase-3)及半胱氨酸天冬氨酸蛋白酶3切割体(cleaved-caspase-3)表达变化;采用CCK-8法检测TE-1细胞经(+)-JQ1(50 nM,24 h)抑制BRD4作用后DDP敏感性的改变。结果TCGA数据解析后结果显示,食管癌肿瘤组织中BRD4的mRNA总体表达水平相较于癌旁正常组织有明显升高[(5.61±0.57)VS(4.80±0.59)],差异有统计意义(P<0.001)。进一步通过对比配对肿瘤和癌旁正常组织样本发现,食管癌患者食管癌组织中BRD4表达水平(5.57±0.31)普遍显著高于其癌旁正常组织的(4.77±0.44),差异有统计学意义(P<0.01)。GEPIA2数据库发现,在食管癌化疗药物耐药形成过程中关键解毒结合酶GSTP1与肿瘤组织中BRD4表达呈正相关(r=0.26,P=0.00029<0.001)。结合靶向siRNA处理Western blot结果显示,siRNA-BRD4处理后食管癌TE-1细胞中BRD4和GSTP1的表达水平较NC组均有明显升高,而siRNA-GSTP1后TE-1细胞中GSTP1表达下调未对BRD4蛋白产生明显影响。进一步采取BRD4靶向抑制剂的梯度浓度处理证实,伴随(+)-JQ1浓度升高TE-1细胞中GSTP1蛋白的表达水平较阴性对照组出现明显下降趋势,而由于(+)-JQ1主要是通过结合于BRD4的溴结构域发挥作用,仅在最高浓度处理(100 nM)组食管癌细胞中BRD4出现表达抑制作用。低浓度的(+)-JQ1(50 nM)处理可引起食管癌TE-1细胞抗凋亡蛋白Bcl-2的表达下调以及凋亡相关蛋白Bax表达上升,但对caspase-3并无明显影响,而在与DDP联合应用时可见caspase-3的活化形式cleaved-caspase-3的相比DDP单独使用组细胞有显著表达上调。Western blot结果表明,(+)-JQ1预处理抑制BRD4的功能可以提高DDP对食管癌细胞的杀伤作用。CCK-8结果显示,食管癌TE-1细胞经抑制BRD4蛋白功能[(+)-JQ1,50 nM,24 h]预处理后可显著提高对化疗药物DDP的敏感性,DMSO对照组DDP的半数抑制浓度(IC50)值为(19.43±0.59)μg/ml,而(+)-JQ1预处理后降至(10.46±0.24)μg/ml,差异有统计学意义(P<0.05)。结论食管癌中高表达的BRD4可能通过GSTP1分子参与DDP敏感性调控。

Association of defective HLA-Ⅰ expression with antigen processing machinery and their association with clinicopathological characteristics in Kazak patients with esophageal cancer

Background It has been confirmed that defective expression of human leukocyte antigen class Ⅰ （HLA-Ⅰ） molecules can contribute to the immune evasion of cancer cells in some types of cancer. The aim of this study was to examine the expression of HLA class Ⅰ antigen and the antigen-processing machinery （APM） components in esophageal squamous cell carcinoma （ESCC） and their role in high risk human papillomavirus （HPV） infection, and to analyze their association with histopathological characteristics in the Kazak ethnic group.Methods A total of 50 formalin-fixed, paraffin-embedded ESCC lesions were collected from the First Affiliated Hospital of Xinjiang Medical University, China. The expression levels of HLA-Ⅰ antigen and APM components were determined by immunohistochemistry; the HPV DNA were detected using polymerase chain reaction （PCR）.Results A high frequency of down-regulation or loss of expression of HLA and APM components were found in esophageal cancer in Kazak people. HLA-Ⅰ, TAP1, CNX, LMP7, Erp57, Tapasin and ERAP1 were down-regulated in 68%,44%, 48%, 40%, 52%, 32% and 20% of ESCC lesions then, respectively. The loss of expression of HLA-Ⅰ antigen was significantly correlated with part of the APM components and positively correlated with high risk HPV16 infection. TAP1,CNX, LMP7, Erp57 and Tapasin loss were significantly associated with tumor grading, lymph node metastasis and depth of invasion （P〈0.05）.Conclusion Our results suggest that APM component defects are a mechanism underlying HLA-Ⅰ antigen down-regulation in ESCC lesions, and indicate that the loss expression of HLA-Ⅰ and APM components will become an important marker of ESCC and analysis of HLA-Ⅰ and APM component expression can provide useful prognostic information for patients with ESCC from the Kazak ethnic group.