Dong Yang, Zhu Guang-Yuan, Hao Lin, Liang Qing, Zhou Jia-He, Shi Zhen-Duo, Yu Hui, Ma Wei-Ming, Fan Tao, Zhang Wen-da, Zang Guang-Hui, Han Cong-Hui
Department of Urology, Xuzhou Central Hospital, Xuzhou, China; Department of Clinical Medicine, Xuzhou Medical University, Xuzhou, China; Medical College of Soochow University, Suzhou, China.
Department of Urology, Xuzhou Central Hospital, Xuzhou, China; Department of Clinical Medicine, Xuzhou Medical University, Xuzhou, China.
Ann Diagn Pathol. 2022 Feb;56:151847. doi: 10.1016/j.anndiagpath.2021.151847. Epub 2021 Oct 29.
Muscle-invasive bladder carcinoma (MIBC) accounts for 25% of newly diagnosed bladder carcinomas (BCs) and presents a high risk of progression and metastasis. This study aimed to identify reliable biomarkers associated with muscle invasion and prognosis to identify potential therapeutic targets for MIBC. Four gene datasets were downloaded from the Gene Expression Omnibus, and the integrated differentially expressed genes (DEGs) were then subjected to gene ontology (GO) terms and pathway enrichment analyses. Correlation analysis between the expression of the top-ranking DEGs and pathological T stages was performed to identify the genes associated with early muscle invasion. The corresponding prognostic values were evaluated, and co-expressed genes mined in the cBioPortal database were loaded into ClueGo in Cytoscape for pathway enrichment analysis. Using data mining from the STRING and TCGA databases, protein-protein interaction and competitive endogenous RNA networks were constructed. In total, 645 integrated DEGs were identified and these were mainly enriched in 26 pathways, including cell cycle, bladder cancer, DNA replication, and PPAR signaling pathway. S100A7 expression was significantly increased from the T2 stage and showed significantly worse overall survival and disease-specific survival in patients with BC. In total, 144 genes co-expressed with S100A7 in BC were significantly enriched in the IL-17 pathway. S100A7 was predicted to directly interact with LYZ, which potentially shows competitive binding with hsa-mir-140 to affect the expression of six lncRNAs in MIBC. In conclusion, high S100A7 expression was predicted to be associated with early muscle invasion and poor survival in patients with BC.
肌层浸润性膀胱癌（MIBC）占新诊断膀胱癌（BC）的25%，具有较高的进展和转移风险。本研究旨在识别与肌层浸润和预后相关的可靠生物标志物，以确定MIBC的潜在治疗靶点。从基因表达综合数据库下载了四个基因数据集，然后对整合的差异表达基因（DEG）进行基因本体（GO）术语和通路富集分析。对排名靠前的DEG表达与病理T分期进行相关性分析，以识别与早期肌层浸润相关的基因。评估相应的预后价值，并将在cBioPortal数据库中挖掘的共表达基因加载到Cytoscape中的ClueGo中进行通路富集分析。利用STRING和TCGA数据库的数据挖掘，构建了蛋白质-蛋白质相互作用和竞争性内源性RNA网络。共鉴定出645个整合的DEG，这些DEG主要富集在26条通路中，包括细胞周期、膀胱癌、DNA复制和PPAR信号通路。S100A7表达从T2期开始显著增加，并且在BC患者中总体生存率和疾病特异性生存率显著更差。在BC中与S100A7共表达的144个基因在IL-17通路中显著富集。预测S100A7与LYZ直接相互作用，LYZ可能与hsa-mir-140竞争性结合，从而影响MIBC中6种lncRNA的表达。总之，预测高S100A7表达与BC患者的早期肌层浸润和不良生存相关。
