食管鳞癌和腺癌转录组差异基因综合分析

Differentially expressed genes in esophageal squamous cell carcinoma and esophageal adenocarcinoma:A comprehensive analysis

目的食管鳞癌和腺癌在分组特征方面有多大的差异目前并不明确。文中旨在分析食管鳞癌、食管腺癌转录组分子特征的差异性。方法下载TCGA数据库中食管鳞癌和腺癌转录组数据,筛选癌及癌旁组织差异表达的RNA(mRNA、lncRNA、miRNA),构建食管鳞癌和腺癌相关的竞争性内源RNA(ceRNA)网络,对重要miRNA进行靶基因预测及GO、KEGG分析,利用生存分析显示食管鳞癌和腺癌共有差异基因。结果ceRNA网络显示:PVT1、LINC00524、miR-204、miR-383、HOXC8、NTRK2等在食管鳞癌和腺癌中均起重要调控作用。miR-204-5p经miRWalk共预测到13227个调控靶基因,在targetscan,miRDB数据库共筛选出232个靶基因。GO功能分析显示38个富集,主要参与细胞-基质粘附的调节、细胞膜投射形态发生、β-连环蛋白结合等过程。KEGG分析显示4个相关通路:Hedgehog信号通路、寿命调节通路、雌激素信号通路、松弛素信号通路。生存分析结果显示,食管鳞癌中与患者生存相关的差异lncRNA包括LINC00261、MLIP-IT1、LINC00504,差异miRNA包括hsa-mir-338,未发现与生存相关的mRNA。食管腺癌中与生存相关的差异lncRNA包括CYP1B1-AS1、HOTAIR,差异mRNA包括IL11、NTRK2、ANGPT2、PBK。食管鳞癌和腺癌共有的差异lncRNA上调占15.4%(150个),下调占26.8%(158个);miRNA上调占24.2%(22个),下调占27.6%(8个);mRNA上调占20.5%(234个),下调占23.7%(418个)。结论食管鳞癌和腺癌存在明显的分子差异,lncRNA、miRNA及mRNA有望为食管癌的治疗和预后预测提供新的靶点与分子标志物。

Objective This study aimed to analyze the differences in the molecular characteristics of transcriptome between esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Methods We obtained transcriptomic data on ESCC and EAC from the TCGA database, screened differentially expressed mRNAs, lncRNAs and miRNAs in cancer and the adjacent tissues, and constructed a network of ESCC- and EAC-related competitive endogenous RNA (ceRNA). We predicted the target genes and performed gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses on important miRNAs, and compared the molecular features of the transcriptomes between ESCC and EAC. Results The ceRNA network analysis showed that PVT1, LINC00524, miR-204, miR-383, HOXC8 and NTRK2 played important regulatory roles in both ESCC and EAC. Totally, 13 227 regulatory target genes were predicted with miR-204-5p via miRWalk and 232 target genes screened from the miRDB database. GO analysis revealed 38 enrichments, mainly involved in the regulation of cell-matrix adhesion, morphogenesis of cell membrane projection, and β-catenin combination, KEGG analysis showed 4 relevant pathways: the hedgehog, life-regulating, estrogen and relaxin signaling pathways, and survival analysis manifested LINC00261, MLIP-IT1 and LINC00504 as survival-related differentially expressed lncRNAs, hsa-mir-338 as differentially expressed miRNA, but no mRNA in ESCC. Survival-related differentially expressed lncRNAs in EAC included CYP1B1-AS1 and HOTAIR, and differentially expressed mRNAs included IL11, NTRK2, ANGPT2 and PBK. Of the differentially expressed lncRNAs in both ESCC and EAC, 150 (15.4%) were up-regulated and 158 (26.8%) down-regulated;of the miRNAs, 22 (24.2%) up-regulated and 8 (27.6%) down-regulated;and of the mRNAs, 234 (20.5%) up-regulated and 418 (23.7%) down-regulated. Conclusion There are significant molecular differences between ESCC and EAC, and the differentially expressed lncRNA, miRNA and mRNA may provide some new targets and molecular markers for the treatment and prognosis of esophageal carcinoma.