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

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e RNA-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,and to 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 in the UCSC Xena database were download.Kaplan⁃Meier survival analysis and correlation analysis were used to iden⁃tify key eRNAs and their regulatory genes as eRNA⁃target gene pairs.The ggboxplot command of R language was used to analyze the correlation between RASSF8⁃AS1 expression and patient clinicopathology,and 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 for validation of RASSF8⁃AS1 expression in normal and gastric adenocarcinoma cell lines.Results The expression level of RASSF8 was significantly cor⁃related with the patient's age,clinical grade,and clinical stage(χ^(2)=4.356、4.166、6.452,P<0.05).The results of RT⁃qPCR showed that compared with normal cells,the expression levels of RASSF8⁃AS1 and RASSF8 in gas⁃tric cancer cells were significantly decreased,and the difference was statistically significant(HR=0.044,95%CI:0.032~0.056,P<0.05).The overall survival rate of patients in the high expression group of RASSF8⁃AS1 was significantly lower than that of the patients in the low expression group,and the difference was statistically significant(P<0.05).GO analysis showed that RASSF8⁃AS1 was involved in various biological processes such as extracellular matrix organization,cell adhesion,regulation of chemical synaptic transmission,and collagen metabolism.In the KEGG pathway analysis,signaling pathways such as interstitial development,extracellular matrix organization,and regulation of membrane potential were enriched.Conclusion RASSF8⁃AS1 is a key eRNA related to survival in gastric cancer,which may become a potential biomarker for early diagnosis and a potential therapeutic target in gastric cancer patients.