C3, C3AR1, HLA-DRA, and HLA-E as potential prognostic biomarkers for renal clear cell carcinoma.
C3, C3AR1, HLA-DRA, and HLA-E as potential prognostic biomarkers for renal clear cell carcinoma.
复制标题
C3、C3AR1、HLA-DRA 和 HLA-E 作为肾透明细胞癌的潜在预后生物标志物。
DOI：
10.21037/tau-20-699
复制
发表时间：
2020-12
影响因子：
2
通讯作者：
Niu H
中科院分区：
文献类型：
--
作者：
Chu G;Jiao W;Yang X;Liang Y;Li Z;Niu H
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。随着科学技术的进步，肾透明细胞癌（KIRC）的生物标志物被大量发现，但其预后价值尚未得到充分研究，因此尚未广泛应用于临床。我们的目的是确定与KIRC患者预后相关的可靠标志物。我们从癌症基因组图谱（TCGA）中获得了72个正常样本和539个肿瘤样本，从基因表达大全（GEO）中获得了23个正常样本和32个肿瘤样本。通过基因本体（GO）和京都基因与基因组百科全书（KEGG）途径分析重叠差异表达基因（ODEG），构建蛋白质-蛋白质相互作用（PPI）网络筛选枢纽基因。采用Kaplan-Meier分析、单因素考克斯分析、多因素考克斯分析、Wilcoxon符号秩检验、Kruskal-Wallis检验和基因集富集分析（GSEA）验证所选标志物的预后价值和功能。分析了基因表达水平与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，并确定C3、C3 AR 1、HLA-E和HLA-E为潜在的肿瘤标志物。各基因的表达与肿瘤免疫细胞浸润、生存率及患者的临床特征密切相关（P<0.05）。C3 AR 1、HLA-E和HLA-AR 1也被证实是KIRC的独立预后因素（P<0.05），并且这些潜在的生物标志物与免疫检查点密切相关。C3、C3 AR 1、HLA-E、HLA-AR-1可作为KIRC的可靠生物标志物，在免疫治疗中可能发挥重要作用，对改善预后有重要意义。
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 C3, C3AR1, HLA-DRA, and HLA-E 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). C3AR1, HLA-DRA, and HLA-E were also verified as independent prognostic factors of KIRC (P<0.05), and all these potential biomarkers had a close correlation with immune checkpoints. C3, C3AR1, HLA-DRA, and HLA-E 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.