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出 处:《临床医学进展》2024年第3期1620-1631,共12页Advances in Clinical Medicine
摘 要:本研究旨在通过生物信息学方法筛选与肾嫌色细胞癌(Chromophobe renal cell carcinoma, chrcc)相关的生物标志物,作为预测chrcc预后的关键基因。GSE15641数据集从Gene Expression Omnibus (GEO)数据库中获取,共鉴定出1153个差异表达基因(DEGs)。随后,检测差异表达基因进行基因本体(GO)注释和京都基因基因组百科全书(KEGG)途径富集分析。此外,利用Cytoscape软件构建蛋白–蛋白相互作用(PPI)网络并可视化鉴定关键基因,包括KRAS、EGFR、EHHADH和CCNB2,根据Kaplan-Meier (K-M)生存分析,CCNB2是唯一重要的核心基因。根据我们的研究结果,CCNB2在The Cancer Genome Atlas(TCGA)-chrcc患者中的表达明显高于正常样本,并且CCNB2在癌症组织中的高表达与不良的临床病理因素有关。CCNB2高表达组与低表达组相比,总生存期(OS)和无进展间期(PFI)明显较差。同时,免疫浸润分析显示CCNB2表达与chrcc患者Th2细胞富集水平呈正相关,CCNB2表达与细胞毒性细胞和DC细胞呈负相关。最后,根据包括CCNB2基因在内的基因集富集分析(Gene Set Enrichment Analysis, GSEA)富集结果,肝癌(HCC)亚类与乳腺癌(BC)的分类存在显著差异。在目前的工作中,CCNB2可以被认为是chrcc的预测性分子标记物和潜在的治疗靶点。The present work aimed to screen biomarkers associated with chromophobe renal cell carcinoma (chrcc) by bioinformatics methods as key genes to predict the prognosis of chrcc. The GSE15641 dataset was acquired from Gene Expression Omnibus (GEO) database, and totally of 1153 differentially expressed genes (DEGs) were identified. Thereafter, DEGs were detected to carry out Gene Ontology (GO) annotation and Kyoto Encyclopedia of Gene and Genome (KEGG) pathway enrichment analysis. Moreover, the protein-protein interaction (PPI) networks were constructed and visualized using Cytoscape software to identify pivotal genes, including KRAS, EGFR, EHHADH and CCNB2, with CCNB2 being identified as the only significant core gene according to Kaplan-Meier (K-M) survival analysis. According to our results, CCNB2 expression was notably higher in The Cancer Genome Atlas (TCGA)-chrcc patients than in normal samples, and the high CCNB2 expression in cancer tissues was associated with adverse clinicopathological factors. The high CCNB2 expression group had markedly poor overall survival (OS) and progression-free interval (PFI) compared with low expression group. Meanwhile, immune infiltration analysis demonstrated a positive correlation between CCNB2 expression and Th2 cells enrichment levels in chrcc patients, and a negative correlation between CCNB2 expression and Cytotoxic cells as well as DC cells. At last, according to the Gene Set Enrichment Analysis (GSEA) enrichment results including CCNB2 gene, there was a significant difference in the classification of hepatocellular carcinoma (HCC) subclass and breast cancer (BC). In the current work, CCNB2 can be considered as a predictive molecular marker and a potential therapeutic target for chrcc.
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