Emerging molecular classiifcations and therapeutic implications for gastric cancer

Gastric cancer (GC) is a highly aggressive and life?threatening malignancy. Even with radical surgical removal and front?line chemotherapy, more than half of GCs locally relapse and metastasize at a distant site. The dismal outcomes relfect the ineffectiveness of a one?size?ifts?all approach for a highly heterogeneous disease with diverse etiological causes and complex molecular underpinnings. The recent comprehensive genomic and molecular proifling has led to our deepened understanding of GC. The emerging molecular classiifcation schemes based on the genetic, epigenetic, and molecular signatures are providing great promise for the development of more effective therapeutic strategies in a more personalized and precise manner. To this end, the Cancer Genome Atlas ( TCGA) research network conducted a comprehensive molecular evaluation of primary GCs and proposed a new molecular classiifcation dividing GCs into four subtypes:Epstein?Barr virus?associated tumors, microsatellite unstable tumors, genomically stable tumors, and tumors with chromosomal instability. This review primarily focuses on the TCGA molecular classiifcation of GCs and discusses the implications on novel targeted therapy strategies. We believe that these fundamental ifndings will sup?port the future application of targeted therapies and will guide our efforts to develop more effcacious drugs to treat human GCs.     

Identification of lncRNAs based on different patterns of immune infiltration in gastric cancer

BackgroundGastric cancer is one of the most common malignant tumors in the world, which brings great challenges to people’s life and health. The purpose of this study was to investigate immune related-lncRNAs and identify new biomarkers for the prognosis of gastric cancer (GC).MethodsWe downloaded data from The Cancer Genome Atlas (TCGA) and used R software to determine the ESTIMATEScore, ImmuneScore, and StromalScore of each tumor sample. We performed prognostic analysis and identified the differentially expressed lnRNAs, which were then used to construct a prognostic model. Among the 44 hub genes in the competitive endogenous RNA (ceRNA) network, 3 differentially expressed genes were verified by qPCR.ResultsBased on the degree of immune infiltration, cluster A had a higher ESTIMATEScore, ImmuneScore, and StromalScore and higher expression levels of PD-L1 (CD274) and CTLA4 than cluster B. Univariate Cox analysis was conducted for these differential lncRNAs, and 57 lncRNAs were found to have prognostic value (P<0.05). gene cluster A had a worse prognosis than gene cluster B (P=0.021). Then, a prognostic model was constructed. The low-risk group had a significantly higher survival rate. Finally, the qPCR results showed that the expression levels of BMPER, PRUNE2, and RBPMS2 were low in GC cell lines.ConclusionsWe identified a risk score of 19 lncRNAs as a prognostic marker of GC. There was a relationship between these 19 prognostic-related lncRNAs and the subtypes of infiltrating immune cells. An approach for predicting the prognosis of GC was therefore provided in this study.     

基于在线分析的磷酸果糖激酶在肺癌中的预后意义探讨

目的:探讨磷酸果糖激酶1（phosphofructokinase 1,PFK1）不同亚型对肺癌预后的预测价值及其可能参与的生物学过程。方法:从癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库中下载表达PFK1不同亚型(PFKP、PFKL和PFKM)表达谱资料及临床信息资料。分别分析这三个基因的表达与肺癌临床病理学参数的相关性及对预后的影响。采用基因集富集分析(Gene Set Enrichment Analysis,GSEA)方法预测关键基因的相关通路。结果:PFKP亚型与肺癌患者预后存在显著相关性（P<0.05）,且高表达患者预后更差。PFKP表达水平与肿瘤浸润深度（T分期）、淋巴结转移数量（N分期）和性别相关。PFKP高表达样本富集了糖酵解、细胞周期、细胞黏附连接等基因集。结论:肺癌中PFKP高表达是预后不良因素,其表达水平可作为预测肺癌患者预后的潜在生物标志物。     

MicroRNA 203对胃癌中EIF5A2表达的影响

目的:研究microRNA 203(miR-203)对胃癌EIF5A2表达的影响,为进一步阐明miR-203与胃癌的关系提供理论基础.方法:分别应用免疫荧光化学和免疫组织化学检测胃癌细胞和组织中EIF5A2的表达;脂质体miR-203转染干预胃癌细胞后,Real time PCR和Western blot检测细胞中EIF5A2 mRNA和蛋白的表达情况.结果:胃癌细胞株SGC7901胞浆中大量表达EIF5A2蛋白,而细胞核中表达较少;胃癌组织中EIF5A2的表达量明显升高;EIF5A2的表达在脂质体miR-203转染干预胃癌细胞后明显受到抑制.结论:胃癌细胞和组织中存在EIF5A2的表达,且miR-203显著抑制了EIF5A2的表达.     

早期胃癌的新型内镜诊断进展

进展性胃癌预后较差,而早期胃癌预后良好,但检出率很低。目前各种新型内镜新技术的应用,使早期胃癌的的诊断大幅提高。现就各种新型内镜技术在早期胃癌的诊断中的应用进行综述。     

Tumor‐associated autoantibody signature for the early detection of gastric cancer

Autoantibodies against tumor‐associated antigens are very attractive biomarkers for the development of noninvasive serological tests for the early detection of cancer because of their specificity and stability in the sera. In our study, we applied T7 phage display‐based serological analysis of recombinant cDNA expression libraries technique to identify a representative set of antigens eliciting humoral responses in patients with gastric cancer (GC), produced phage–antigen microarrays and exploited them for the survey of autoantibody repertoire in patients with GC and inflammatory diseases. We developed procedures for data normalization and cutoff determination to define sero‐positive signals and ranked them by the signal intensity and frequency of reactivity. To identify autoantibodies with the highest diagnostic value, a 1,150‐feature microarray was tested with sera from 100 patients with GC and 100 cancer‐free controls, and then the top‐ranked 86 antigens were used for the production of focused array that was tested with an independent validation set comprising serum samples from 235 patients with GC, 154 patients with peptic ulcer and gastritis and 213 healthy controls. The receiver operating characteristic curve analysis showed that 45‐autoantibody signature could discriminate GC and healthy controls with area under the curve (AUC) of 0.79 (59% sensitivity and 90% specificity), GC and peptic ulcer with AUC of 0.76 and GC and gastritis with AUC of 0.64. Moreover, it could detect early GC with equal sensitivity than advanced GC. Interestingly, the autoantibody production did not correlate with histological type, H. pylori status, grade, localization and size of the primary tumor, whereas it appeared to be associated with the metastatic disease.     

老年人特殊型早期胃癌的特点及内镜诊断

本文报道了２９例老年人特殊型早期胃癌，包括多发癌３例，＂一点癌＂４例，胃炎样癌２２例，探讨了老年人的临床特点，各型内镜下表现及具体操作方法，以提高老年人早期癌的检出率。     

早期胃癌淋巴结转移及临床意义

淋巴结转移是影响早期胃癌手术方式选择和预后的重要因素,对其转移规律和特点的认识及检测方法的掌握对于合理开展缩小手术至关重要。运用免疫组化和逆转录聚合酶链反应技术对早期胃癌前哨淋巴结检测不仅可以了解淋巴结站的转移特点、规律,而且可以发现微转移,从而指导术中淋巴结清扫范围而选择合理术式,避免标准根治术淋巴结清扫和扩大的手术方式对机体造成不必要的损害,减少手术创伤和术后并发症的出现,提高患者术后生存质量。     

Comparison and applicability of molecular classifications for gastric cancer

Gastric Cancer (GC) is a complex and heterogeneous disease, which represents a global health concern. Despite advances in prevention, diagnosis, and therapy, GC is still a leading cause of cancer-related death. Over the last decade, several clinical trials have tested novel agents for advanced GC with mostly disappointing results. Heterogeneity, the absence of molecular selection in clinical trials and powerless predictive biomarkers may be potential explanations. Different molecular classification proposals for GC based on the genetic, epigenetic, and molecular signatures have been published. Molecular characterization of GC may offer new tools for more effective therapeutic strategies, such as the development of therapies for specifically well-defined sets of patients as well as the use of new clinical trial designs, which will ultimately lead to an improvement of medical management of this disease. However, the possibilities of implementation of GC molecular classifications on daily practice and their therapeutic implications remain challenging to date. In this review, we will describe and compare these GC molecular classifications, focusing on their main characteristics as the basis for their potential therapeutic implications and strategies for their clinical application.Key Message: A better understanding of gastric cancer molecular characteristics may lead to further improvements in treatment and outcomes for patients with the disease.     

67例早期胃癌临床病理特征及预后分析

目的：研究早期胃癌患者的临床病理特征及预后因素.方法：回顾性分析我院67例早期胃癌根治术标本的肿瘤直径、浸润深度、肉眼分型、组织学分型、淋巴结数目、淋巴结转移等资料.并对患者进行随访及预后分析.结果：早期胃癌发病高峰为40-59岁,以男性多见.大体分型以凹陷型、浅表型为主,组织学分型以管状腺癌为主,12例伴胃周淋巴结转移,5年生存率为95%,粘膜内癌不伴有胃周淋巴结转移者5年生存率为100%.结论：提高早期胃癌的检出率,降低胃癌死亡率.     

胃癌特异染色剂对早期胃癌的诊断价值

目的探讨一种胃癌特异染色剂对早期胃癌的诊断价值。方法用经20例预试验筛选而最终确定的自配核染色剂进行活体模拟染色试验。标本采自经胃镜及病理确诊的195例胃癌患者。结果胃癌组织均在15％～20％浓度染色剂中短时间（≤30s）内着色，而癌周胃黏膜组织60s及以后才开始着色，两者比较差异有统计学意义（P〈0．05）。不同病理类型的胃癌在不同浓度染色剂下显色时间有所不同。结论自配核染色剂在特定浓度、短时间内可使胃癌组织特异染色，使肉眼可区别癌周黏膜组织，有望成为一种新型的胃癌特异染色剂，用于色素内镜诊断早期胃癌。     

Risk of second malignancies after surgical treatment for early gastric cancer

Received for publication on March 16, 1998; accepted on Dec. 1, 1998     

2010-2018年甘肃省胃癌发病死亡比较分析

目的:分析2010-2018年全球、亚洲、东亚地区、中国、甘肃省胃癌发病、死亡情况.为中国及甘肃省胃癌预防控制工作提供流行病学依据.方法:中国人口标准化率(中标率)采用2000年全国人口普查的标准人口年龄构成,世界人口标准化率(世标率)采用Segi's标准人口年龄构成.由GLOBOCAN数据库获得全球、亚洲、东亚地区、...     

染色内镜在早期胃癌诊断中的价值

目的:评价应用亚甲蓝染色方法的内镜检测对早期胃癌的诊断价值。方法:对我院2011年1月-2013年6月298例进行胃镜检查的胃癌可疑患者,随机进行常规取检或亚甲蓝染色后取检,其中常规取检142例,染色后取检156例,计算不同方法对早期胃癌诊断的发现率,对比两种方法有无差别。结果:常规取检发现胃癌10例,发现率7.04%。染色后取检发现胃癌19例,发现率12.18%,虽然统计学无显著性差异,但两组阳性率还是有一定差距,考虑到肿瘤的危害性,只要能提高早期诊断的方法都值得重视。结论:染色内镜较常规内镜能提高早期胃癌的检出率,值得进一步深入探讨。