Peng Rui, Wang Yahui, Mao Likai, Fang Fang, Guan Han
Department of Urology, First Affiliated Hospital of Bengbu Medical College, Bengbu, People's Republic of China.
Department of Urology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Shenshan Central Hospital, Shanwei, People's Republic of China.
Cancer Manag Res. 2020 Dec 30;12:13437-13449. doi: 10.2147/CMAR.S276818. eCollection 2020.
Renal cell carcinoma (RCC) is one of the most common malignancies globally, among which clear cell carcinoma (ccRCC) accounts for 85-90% of all pathological types. This study aims to screen out potential genes in metastatic ccRCC so as to provide novel insights for ccRCC treatment.
GSE53757 and GSE84546 datasets in the Gene Expression Omnibus (GEO) were profiled to identify differentially expressed genes (DEGs) from ccRCC samples with or without metastasis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and the gene ontology (GO) analysis were performed to analyze pathway enrichment and functional annotation of DEGs. Protein-protein interaction (PPI) network was constructed, and survival analysis was conducted to evaluate the clinical values of the identified hub genes. In vitro loss-of-function assays were performed to explore the biological roles of these genes.
The bioinformatic analysis indicated that 312 DEGs were identified, including 148 upregulated genes and 164 downregulated ones. Using PPI and Cytoscape, 10 hub genes were selected (, , , , , , , , , and ) from DEGs which might be closely related with ccRCC metastasis. In Kaplan-Meier analysis, three potential prognostic biomarkers (, and ) were identified. Finally, cell proliferative and invasive assays further verified that , and were associated with the proliferation and invasion of ccRCC cells.
Our results demonstrated that metastatic ccRCC was partially attributed to the aberrant expression of , and , and more personalized therapeutic approaches should be explored targeting these hub genes.
肾细胞癌（RCC）是全球最常见的恶性肿瘤之一，其中透明细胞癌（ccRCC）占所有病理类型的85 - 90%。本研究旨在筛选转移性ccRCC中的潜在基因，为ccRCC治疗提供新的见解。
对基因表达综合数据库（GEO）中的GSE53757和GSE84546数据集进行分析，以鉴定有或无转移的ccRCC样本中的差异表达基因（DEGs）。进行京都基因与基因组百科全书（KEGG）和基因本体（GO）分析，以分析DEGs的通路富集和功能注释。构建蛋白质 - 蛋白质相互作用（PPI）网络，并进行生存分析以评估所鉴定的枢纽基因的临床价值。进行体外功能丧失试验以探索这些基因的生物学作用。
生物信息学分析表明，共鉴定出312个DEGs，包括148个上调基因和164个下调基因。使用PPI和Cytoscape软件，从可能与ccRCC转移密切相关的DEGs中筛选出10个枢纽基因（、、、、、、、、和）。在Kaplan - Meier分析中，鉴定出三个潜在的预后生物标志物（、和）。最后，细胞增殖和侵袭试验进一步证实、和与ccRCC细胞的增殖和侵袭有关。
我们的结果表明，转移性ccRCC部分归因于、和的异常表达，应针对这些枢纽基因探索更具个性化的治疗方法。
