Chu Guangdi, Jiao Wei, Yang Xuecheng, Liang Ye, Li Zhiqiang, Niu Haitao
Department of Urology, The Affiliated Hospital of Qingdao University, Qingdao, China.
The Affiliated Hospital of Qingdao University & The Biomedical Sciences Institute of Qingdao University (Qingdao Branch of SJTU Bio-X Institutes), Qingdao University, Qingdao, China.
Transl Androl Urol. 2020 Dec;9(6):2640-2656. doi: 10.21037/tau-20-699.
Prognostic biomarkers play a vital role in the early detection of the cancer and assessment of prognosis. With advances in technology, a large number of biomarkers of kidney renal clear cell carcinoma (KIRC) have been discovered, but their prognostic value has not been fully investigated, and thus have not been widely used in clinical practice. We aimed to identify the reliable markers associated with the prognosis of KIRC patients.
We obtained 72 normal samples and 539 tumor samples from The Cancer Genome Atlas (TCGA), and 23 normal samples and 32 tumor samples from the Gene Expression Omnibus (GEO). Overlapping differentially expressed genes (ODEGs) were analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, followed by construction of a protein-protein interaction (PPI) network to screen hub genes. Kaplan-Meier analysis, univariate Cox analysis, multivariate Cox analysis, Wilcoxon signed-rank test, Kruskal-Wallis test, and gene set enrichment analysis (GSEA) were performed to verify the prognostic value and function of the markers we selected. The relationships among gene expression level, tumor immune cell infiltration, and immune-checkpoints were also analyzed.
A total of 910 genes were screened out, and , and were identified as potential tumor markers. The expression of each gene was closely associated with tumor immune cell infiltration, survival rate, and the patients' clinical characteristics (P<0.05). , , and were also verified as independent prognostic factors of KIRC (P<0.05), and all these potential biomarkers had a close correlation with immune checkpoints.
, , , and could be reliable biomarkers of KIRC and may have a significant contribution to make in immunotherapy, thus playing an important role in the improvement of prognosis.
预后生物标志物在癌症的早期检测和预后评估中起着至关重要的作用。随着技术的进步,已经发现了大量肾透明细胞癌(KIRC)的生物标志物,但其预后价值尚未得到充分研究,因此尚未在临床实践中广泛应用。我们旨在确定与KIRC患者预后相关的可靠标志物。
我们从癌症基因组图谱(TCGA)获得了72个正常样本和539个肿瘤样本,从基因表达综合数据库(GEO)获得了23个正常样本和32个肿瘤样本。通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析对重叠的差异表达基因(ODEGs)进行分析,随后构建蛋白质-蛋白质相互作用(PPI)网络以筛选枢纽基因。进行Kaplan-Meier分析、单因素Cox分析、多因素Cox分析、Wilcoxon符号秩检验、Kruskal-Wallis检验和基因集富集分析(GSEA)以验证我们选择的标志物的预后价值和功能。还分析了基因表达水平、肿瘤免疫细胞浸润和免疫检查点之间的关系。
共筛选出910个基因, 、 和 被确定为潜在的肿瘤标志物。每个基因的表达与肿瘤免疫细胞浸润、生存率和患者的临床特征密切相关(P<0.05)。 、 和 也被验证为KIRC的独立预后因素(P<0.05),并且所有这些潜在的生物标志物都与免疫检查点密切相关。
、 、 和 可能是KIRC的可靠生物标志物,并且可能在免疫治疗中做出重大贡献,从而在改善预后方面发挥重要作用。