增强子RNA RASSF8-AS1在胃腺癌中的临床意义与分子机制  

Clinical significance and molecular mechanism of enhancer RNA RASSF8⁃AS1 in gastric adenocarcinoma

作　　者：马甜甜 朱翠雯 李东旭 张晓洋 喻明霞[1] MA Tiantian;ZHU Cuiwen;LI Dongxu;ZHANG Xiaoyang;YU Mingxia(Department of Laboratory Medicine,Zhongnan Hospital of Wuhan University,Wuhan,Hubei,China,430071)

机构地区：[1]武汉大学中南医院检验科,湖北武汉430071

出　　处：《分子诊断与治疗杂志》2024年第3期433-437,共5页Journal of Molecular Diagnostics and Therapy

基　　金：国家自然科学基金(81472033、30901308);湖北省卫生健康科研基金资助(WJ2019M203);湖北省卫生和计划生育委员会联合基金项目(WJ2018H0028);湖北省卫生和计划生育委员会青年人才项目(WJ2015Q021);武汉市应用基础研究(2017060201010171);武汉大学中南医院科技创新培育基金(cxpy2018031、cxpy20160054);武汉大学大学生创新项目(MS2017045、S2018301747)。

摘　　要：目的 探究增强子RNA RASSF8-AS1在胃腺癌(STAD)中的表达和关键靶基因预测,分析RASSF8-AS1与临床病理特征、预后的关系,探索RASSF8-AS1在STAD发生发展中的作用机制。方法在UCSC Xena数据库中下载33类肿瘤的表达数据、生存数据和临床数据。采用Kaplan-Meier生存分析和相关性分析确定关键eRNA及其调控基因为eRNA-靶基因对。使用R语言ggboxplot命令分析RASSF8-AS1表达与患者临床病理的相关性,利用GO和KEGG富集分析探索RASSF8-AS1在STAD中参与的信号途径。使用逆转录聚合酶链式反应(RT-qPCR)验证RASSF8-AS1在正常和胃腺癌细胞系中的表达量。结果 RASSF8-AS1的表达水平与患者的年龄、临床分级、临床分期显著相关(χ^(2)=4.356、4.166、6.452,P均<0.05)。RT-qPCR结果表明,与正常细胞相比,胃癌细胞中RASSF8-AS1和RASSF8的表达水平显著降低,差异有统计学意义(HR=0.044,95%CI:0.032~0.056,P<0.05)。RASSF8-AS1高表达组患者的总体生存率显著低于低表达组患者,差异有统计学意义(P<0.05)。GO分析结果表明,RASSF8-AS1参与了细胞外基质组织构建、细胞黏附、化学突触传递的调节、胶原代谢等多种生物过程。KEGG通路分析中,间质发展、细胞外基质组织、膜电位的调节等信号途径被富集。结论 RASSF8-AS1是胃癌中与生存相关的关键eRNA,可能成为胃癌患者早期诊断的潜在生物标志物和潜在的治疗靶点。Objective To explore the expression and key target gene prediction of enhancer RNA RASSF8-AS1 in stomach adenocarcinoma(STAD),and to analyze the relationship between RASSF8-AS1 and clinicopathological features and prognosis,as well as explore the mechanism of RASSF8-AS1 in the occurrence and development of STAD.Methods Expression data,survival data,and clinical data for 33 tumor types from the UCSC Xena database were download.Kaplan-Meier survival analysis and correlation analysis were used to identify key eRNAs and their regulatory genes as eRNA-target gene pairs.The ggboxplot command of the R language was used to analyze the correlation between RASSF8-AS1 expression and patient clinicopatholo-gy.Additionally,GO and KEGG enrichment analysis were used to explore the signaling pathways involved in RASSF8-AS1 in STAD.Reverse transcription polymerase chain reaction(RT-qPCR)was used to validate the expression of RASSF8-AS1 in normal and gastric adenocarcinoma cell lines.Results The expression level of RASSF8 was significantly correlated with the patient's age,clinical grade,and clinical stage(χ^(2)=4.356,4.166,6.452,P<0.05).RT-qPCR results showed that compared with normal cells,the expression levels of RASSF8-AS1 and RASSF8 in gastric cancer cells were significantly decreased,with a statistically significant difference(HR=0.044,95%CI:0.032~0.056,P<0.05).The overall survival rate of patients in the high ex-pression group of RASSF8-AS1 was significantly lower than that of the patients in the low expression group,with a statistically significant difference(P<0.05).GO analysis showed that RASSF8-AS1 was involved in vari-ous biological processes such as extracellular matrix organization,cell adhesion,regulation of chemical synap-tic transmission,and collagen metabolism.In the KEGG pathway analysis,signaling pathways such as intersti-tial development,extracellular matrix organization,and regulation of membrane potential were enriched.Conclusion RASSF8-AS1 is a crucial survival-related eRNA in gastric cancer and could serv

关 键 词：胃腺癌 RASSF8-AS1 eRNA 预后 

分 类 号：R735.2[医药卫生—肿瘤]