Li Xin, Ma Cuiyan
Department of Rehabilitation Medicine, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine Tsinghua University Beijing China.
Department of Computer Science and Technology, BNRist, RIIT, Institute of Internet Industry Tsinghua University Beijing China.
Health Sci Rep. 2022 Oct 17;5(6):e878. doi: 10.1002/hsr2.878. eCollection 2022 Nov.
Chromophobe renal cell carcinoma (chRCC) is the third common pathological subtype in renal cancers. However, the underlying mechanisms of specific genetic characteristics of chRCC are currently unclear. In this study, protein expression profiles, gene ontology (GO), and survival plots were provided by integrated bioinformatics analysis to investigate key genes associated with the mechanism of tumorigenesis and prognosis of chRCC.
The chRCC data set of gene expression profiles and clinical data were obtained from the gdc-client (https://portal.gdc.cancer.gov) deposited on The Cancer Genome Atlas (TCGA) data portal. Differentially expressed genes (DEGs) in chRCC, compared with normal samples, were analyzed by R packages "DESeq2," "edgeR," and "limma." Heat maps, volcano plots, and principal component analysis (PCA) were performed for integrated analyses. GUniGO, mutant analysis, and survival plots were performed by R packages. A protein-protein interaction (PPI) network was generated and analyzed by R packages, online String software, and Cytoscape software. Survival analysis and gene expressing comparison in tumor and normal samples were used to detect the core genes of chRCC. Furthermore, the top interacting proteins were reanalyzed.
A total of 306 upregulated genes and 678 downregulated genes were identified by a Venn diagram. Ten hub genes were extracted from PPI network. Furthermore, Alpha-2-Heremans-Schmid-glycoprotein (AHSG), one of 10 hub genes, was found to be associated with chRCC, and had a big difference in expression between survival and dead events. AHSG could predict potential prognostic and may be a diagnostic biomarker in chRCC.
This study illustrated that AHSG may be a potential therapeutic target and prognostic genetic marker for chRCC.
嫌色肾细胞癌(chRCC)是肾癌中第三常见的病理亚型。然而,chRCC特定遗传特征的潜在机制目前尚不清楚。在本研究中,通过综合生物信息学分析提供蛋白质表达谱、基因本体论(GO)和生存曲线,以研究与chRCC肿瘤发生机制和预后相关的关键基因。
从存储于癌症基因组图谱(TCGA)数据门户的gdc-client(https://portal.gdc.cancer.gov)获取chRCC基因表达谱数据集和临床数据。使用R包“DESeq2”、“edgeR”和“limma”分析chRCC与正常样本相比的差异表达基因(DEG)。进行热图、火山图和主成分分析(PCA)以进行综合分析。通过R包进行基因本体论(GO)分析、突变分析和生存曲线分析。使用R包、在线String软件和Cytoscape软件生成并分析蛋白质-蛋白质相互作用(PPI)网络。通过生存分析和肿瘤与正常样本中的基因表达比较来检测chRCC的核心基因。此外,对顶级相互作用蛋白进行重新分析。
通过维恩图共鉴定出306个上调基因和678个下调基因。从PPI网络中提取了10个枢纽基因。此外,发现10个枢纽基因之一的α-2-赫里曼斯-施密德糖蛋白(AHSG)与chRCC相关,并且在生存和死亡事件之间的表达存在很大差异。AHSG可以预测chRCC的潜在预后,可能是一种诊断生物标志物。
本研究表明,AHSG可能是chRCC的潜在治疗靶点和预后遗传标志物。