基于综合生物信息学分析鉴定膀胱癌进展和预后相关的枢纽基因。
Identification of Hub Genes Associated with Progression and Prognosis of Bladder Cancer by Integrated Bioinformatics Analysis.
机构信息
Department of Clinical Medicine, School of Basic Medicine, Jiujiang University, 332000 Jiujiang, Jiangxi, China.
Department of Gynecology and Obstetrics, Zhongnan Hospital of Wuhan University, 430071 Wuhan, Hubei, China.
出版信息
Arch Esp Urol. 2022 Nov;75(9):779-790. doi: 10.56434/j.arch.esp.urol.20227509.114.
BACKGROUND
Bladder cancer (BLCA) is an extremely common carcinoma of the urinary system that has a high incidence of relapse. Although intensive studies have investigated its pathology in the past decades, there are significant knowledge gaps regarding the characterization of the molecular processes underlying the progression of disease and consequently its prognosis. The purpose of current research was to identify significant genes that could serve as prognostic and progression biomarkers.
METHODS
Gene expression profiles were downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database. Differential gene expression analysis (DGEA) and weighted gene co-expression network analysis (WGCNA) were conducted to recognize differential co-expression genes. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed to explore gene function. Moreover, protein-protein interactions (PPI) network, overall survival (OS) and disease-free survival (DFS) were used to identify survival-related hub genes. Additionally, associations between these gene's expression and clinical parameters were determined. Finally, the Human Protein Atlas (HPA) database and qRT-PCR were used to validate gene's expression.
RESULTS
About 124 differential co-expression genes were identified. These genes were mainly enriched in muscle system process and muscle contraction (biological process, BP), contractile fiber, myofibril, sarcomere, focal adhesion and cell-substrate junction (cellular component, CC) and actin binding (molecular function, MF) in GO enrichment analysis, while enriched in vascular smooth muscle contraction, focal adhesion, cardiac muscle contraction, hypertrophic cardiomyopathy, dilated cardiomyopathy and regulation of actin cytoskeleton in KEGG analysis. Furthermore, five survival-related hub genes (MYH11, ACTA2, CALD1, TPM1, MYLK) were identified via OS and DFS. In addition, these survival-related gene's expression was correlated with grade, stage and TNM stage. Finally, all survival-related hub genes were determined to be down-regulated in BLCA tissues by qRT-PCR and HPA databases.
CONCLUSIONS
Our current study verified five new key genes in BLCA, which may participate in the prognosis and progression and serve as novel biomarkers of BLCA.
背景
膀胱癌（BLCA）是一种极其常见的泌尿系统癌，其复发率很高。尽管过去几十年已经对其病理学进行了深入研究，但在疾病进展及其预后的分子过程特征方面仍存在重大知识空白。本研究的目的是确定可作为预后和进展生物标志物的重要基因。
方法
从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）下载基因表达谱。进行差异基因表达分析（DGEA）和加权基因共表达网络分析（WGCNA）以识别差异共表达基因。进行基因本体论（GO）富集分析和京都基因与基因组百科全书（KEGG）通路分析以探讨基因功能。此外，使用蛋白质-蛋白质相互作用（PPI）网络、总生存期（OS）和无病生存期（DFS）来识别与生存相关的枢纽基因。此外，还确定了这些基因的表达与临床参数之间的关联。最后，使用人类蛋白质图谱（HPA）数据库和 qRT-PCR 来验证基因的表达。
结果
鉴定出约 124 个差异共表达基因。这些基因在 GO 富集分析中主要富集在肌肉系统过程和肌肉收缩（生物学过程，BP）、收缩纤维、肌原纤维、肌节、黏附斑和细胞-基质连接（细胞成分，CC）和肌动蛋白结合（分子功能，MF），而在 KEGG 分析中则富集在血管平滑肌收缩、黏附斑、心肌收缩、肥厚型心肌病、扩张型心肌病和肌动蛋白细胞骨架调节。此外，通过 OS 和 DFS 鉴定了五个与生存相关的枢纽基因（MYH11、ACTA2、CALD1、TPM1、MYLK）。此外，这些与生存相关基因的表达与分级、分期和 TNM 分期相关。最后，通过 qRT-PCR 和 HPA 数据库确定所有与生存相关的枢纽基因在 BLCA 组织中均下调。
结论
本研究验证了 BLCA 中的五个新关键基因，它们可能参与预后和进展，并可作为 BLCA 的新型生物标志物。
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