Zhang Bo, Wu Qiong, Wang Ziheng, Xu Ran, Hu Xinyi, Sun Yidan, Wang Qiuhong, Ju Fei, Ren Shiqi, Zhang Chenlin, Qin Lin, Ma Qianqian, Zhou You Lang
Medical School of Nantong University, Nantong, P.R. China.
The Hand Surgery Research Center, Department of Hand Surgery, Affiliated Hospital of Nantong University, Nantong, P.R. China.
Mol Genet Genomic Med. 2019 May;7(5):e607. doi: 10.1002/mgg3.607. Epub 2019 Feb 21.
Kidney renal clear cell carcinoma (KIRC) is the most common subtype of renal tumor. However, the molecular mechanisms of KIRC pathogenesis remain little known. The purpose of our study was to identify potential key genes related to the occurrence and prognosis of KIRC, which could serve as novel diagnostic and prognostic biomarkers for KIRC.
Three gene expression profiles from gene expression omnibus database were integrated to identify differential expressed genes (DEGs) using limma package. Enrichment analysis and PPI construction for these DEGs were performed by bioinformatics tools. We used Gene Expression Profiling Interactive Analysis (GEPIA) database to further analyze the expression and prognostic values of hub genes. The GEPIA database was used to further validate the bioinformatics results. The Connectivity Map was used to identify candidate small molecules that could reverse the gene expression of KIRC.
A total of 503 DEGs were obtained. The PPI network with 417 nodes and 1912 interactions was constructed. Go and KEGG pathway analysis revealed that these DEGs were most significantly enriched in excretion and valine, leucine, and isoleucine degradation, respectively. Six DEGs with high degree of connectivity (ACAA1, ACADSB, ALDH6A1, AUH, HADH, and PCCA) were selected as hub genes, which significantly associated with worse survival of patients. Finally, we identified the top 20 most significant small molecules and pipemidic acid was the most promising small molecule to reverse the KIRC gene expression.
This study first uncovered six key genes in KIRC which contributed to improving our understanding of the molecular mechanisms of KIRC pathogenesis. ACAA1, ACADSB, ALDH6A1, AUH, HADH, and PCCA could serve as the promising novel biomarkers for KIRC diagnosis, prognosis, and treatment.
肾透明细胞癌（KIRC）是最常见的肾肿瘤亚型。然而，KIRC发病机制的分子机制仍鲜为人知。我们研究的目的是鉴定与KIRC发生和预后相关的潜在关键基因，这些基因可作为KIRC新的诊断和预后生物标志物。
整合来自基因表达综合数据库的三个基因表达谱，使用limma软件包鉴定差异表达基因（DEG）。通过生物信息学工具对这些DEG进行富集分析和蛋白质-蛋白质相互作用（PPI）网络构建。我们使用基因表达谱交互分析（GEPIA）数据库进一步分析枢纽基因的表达和预后价值。GEPIA数据库用于进一步验证生物信息学结果。利用连接图谱鉴定可逆转KIRC基因表达的候选小分子。
共获得503个DEG。构建了一个包含417个节点和1912个相互作用的PPI网络。基因本体（GO）和京都基因与基因组百科全书（KEGG）通路分析显示，这些DEG分别在排泄以及缬氨酸、亮氨酸和异亮氨酸降解中显著富集。选择六个连接度高的DEG（ACAA1、ACADSB、ALDH6A1、AUH、HADH和PCCA）作为枢纽基因，它们与患者较差的生存率显著相关。最后，我们鉴定出前20个最显著的小分子，吡哌酸是最有希望逆转KIRC基因表达的小分子。
本研究首次揭示了KIRC中的六个关键基因，有助于提高我们对KIRC发病机制分子机制的理解。ACAA1、ACADSB、ALDH6A1、AUH、HADH和PCCA可作为KIRC诊断、预后和治疗有前景的新型生物标志物。
