肺腺癌LINC00982的TCGA表达谱分析及预后意义

TCGA EXPRESSION PROFILE OF LINC00982 AND ITS PROGNOSTIC SIGNIFICANCE IN LUNG ADENOCARCINOMA

目的通过TCGA数据库对肺腺癌(LUAD)病人相关测序资料进行分析,探讨与LUAD预后相关的长链非编码RNA(LncRNAs)。方法从TCGA数据库下载LUAD的基因表达资料及临床信息,使用edge R包进行差异分析,Survival包行预后分析,加权基因共表达网络分析(WGCNA)包构建共表达网络,寻找与生存显著相关的基因模块,ClusterProfiler包对目标模块的mRNA进行基因本体论(GO)注释和KEGG富集分析。结果共筛选得到15473个差异表达基因(DEGs),进一步筛选得到187个差异表达的LncRNAs(DELncRNAs),其中80个DELncRNAs表达上调,107个DELncRNAs表达下调。将DELncRNAs纳入Cox危险比例回归模型进行分析,得到影响LUAD病人预后的15个LncRNAs。Kaplan Meier分析验证显示,Cox分析结果中低风险的LUAD病人较高风险者拥有更长的生存期。通过WGCNA生成40个模块,其中violet模块与生存相关性最高(r=0.680,P<0.05);violet模块中的LncRNAs与预后相关的DELncRNAs取交集,通过筛选得到LINC00982。对violet模块的mRNA进行富集分析后显示,LINC00982在血管生成、白细胞介素-6(IL-6)、淋巴免疫等有关的生物学过程(BP)中显著富集,在核染色体等有关的细胞成分(CC)中占比增加,与嘧菌酯域结合等有关的分子功能(MF)有关,主要参与IL-17、PD-L1等相关的信号通路。Pearson分析显示,PRDM16表达水平随LINC00982表达上调而升高(r=0.897,P<0.001),可能为LINC00982的靶基因。结论LINC00982可能为预测LUAD病人预后的生物学标志物,通过靶控PRDM16参与LUAD的发生发展。

Objective To investigate the long non-coding RNAs(lncRNAs)associated with the prognosis of lung adenocarcinoma(LUAD)by analyzing the sequencing data of LUAD patients based on the TCGA database.Methods Gene expression data and clinical information of LUAD were downloaded from the TCGA database.The edge R package was used for differen-tial analysis;Survival package was used to perform a prognostic analysis;weighted gene co-expression network analysis(WGCNA)package was used to construct co-expression networks and identify the gene modules significantly associated with survival;ClusterProfiler package was used to perform Gene Ontology(GO)annotation and Kyoto Encyclopedia of Whole Genes and Genomes(KEGG)enrichment analysis of the mRNAs of target modules.Results A total of 15473 differentially expressed genes were screened out,and 187 differentially expressed LncRNAs(DELncRNAs)were obtained by further screening,among which 80 LncRNAs were upregulated and 107 were downregulated.The DELncRNAs were included in the Cox proportional-hazards regression model and 15 LncRNAs were found to affect the prognosis of LUAD patients.The Kaplan-Meier analysis showed that the low-risk LUAD patients determined by the Cox analysis had a longer survival time than their high-risk LUAD counterparts.A total of 40 modules were generated by WGCNA,among which the violet module had the highest correlation with survival(r=0.680,P<0.05).The intersection of the LncRNAs in the violet module and the DELncRNAs associated with prognosis was taken to obtain LINC00982.The enrichment analysis of the mRNAs of the violet module revealed that LINC00982 was significantly enriched in the biological processes associated with angiogenesis,interleukin-6,and lymphatic immunity,with an increased proportion in related cellular components including nuclear chromosomes,and it was associated with the molecular functions including pyrimethane-domain binding and was mainly involved in the signaling pathways associated with IL-17 and PD-L1.The Pearson test showed that the expression level of PRDM16 increased with the upregulation of LINC00982 expression(r=0.897,P<0.001),suggesting that PRDM16 might be the target gene of LINC00982.Conclusion LINC00982 may be used as a biological marker for predicting the prognosis of LUAD patients and it may be involved in the development and progression of LUAD by targeting PRDM16.