Department of Urology, Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Haikou, Hainan, China.
Laboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China.
Mol Genet Genomic Med. 2020 Apr;8(4):e1159. doi: 10.1002/mgg3.1159. Epub 2020 Feb 3.
Clear cell renal cell carcinoma (ccRCC) is the most common pathological subtype of renal cell carcinoma. Bioinformatics analyses were used to screen candidate genes associated with the prognosis and microenvironment of ccRCC and elucidate the underlying molecular mechanisms of action.
The gene expression profiles and clinical data of ccRCC patients were downloaded from The Cancer Genome Atlas database. The ESTIMATE algorithm was used to compute the immune and stromal scores of patients. Based on the median immune/stromal scores, all patients were sorted into low- and high-immune/stromal score groups. Differentially expressed genes (DEGs) were extracted from high- versus low-immune/stromal score groups and were described using functional annotations and protein-protein interaction (PPI) network.
Patients in the high-immune/stromal score group had poorer survival outcome. In total, 95 DEGs (48 upregulated and 47 downregulated genes) were screened from the gene expression profiles of patients with high immune and stromal scores. The genes were primarily involved in six signaling pathways. Among the 95 DEGs, 43 were markedly related to overall survival of patients. The PPI network identified the top 10 hub genes-CD19, CD79A, IL10, IGLL5, POU2AF1, CCL19, AMBP, CCL18, CCL21, and IGJ-and four modules. Enrichment analyses revealed that the genes in the most important module were involved in the B-cell receptor signaling pathway.
This study mainly revealed the relationship between the ccRCC microenvironment and prognosis of patients. These results also increase the understanding of how gene expression patterns can impact the prognosis and development of ccRCC by modulating the tumor microenvironment. The results could contribute to the search for ccRCC biomarkers and therapeutic targets.
透明细胞肾细胞癌(ccRCC)是肾细胞癌最常见的病理亚型。本研究通过生物信息学分析筛选与 ccRCC 预后和微环境相关的候选基因,并阐明其潜在的作用机制。
从癌症基因组图谱数据库中下载 ccRCC 患者的基因表达谱和临床数据。采用 ESTIMATE 算法计算患者的免疫和基质评分。根据免疫/基质评分的中位数,将所有患者分为低免疫/基质评分组和高免疫/基质评分组。从高免疫/基质评分组和低免疫/基质评分组的基因表达谱中提取差异表达基因(DEGs),并进行功能注释和蛋白质-蛋白质相互作用(PPI)网络分析。
高免疫/基质评分组患者的生存预后较差。从高免疫和基质评分患者的基因表达谱中筛选出 95 个 DEGs(48 个上调基因和 47 个下调基因)。这些基因主要参与了六个信号通路。在 95 个 DEGs 中,有 43 个与患者的总生存率显著相关。PPI 网络鉴定出 10 个关键基因(CD19、CD79A、IL10、IGLL5、POU2AF1、CCL19、AMBP、CCL18、CCL21 和 IGJ)和四个模块。富集分析表明,最重要模块中的基因参与了 B 细胞受体信号通路。
本研究主要揭示了 ccRCC 微环境与患者预后的关系。这些结果还增加了对基因表达模式如何通过调节肿瘤微环境影响 ccRCC 预后和发展的理解。研究结果有助于寻找 ccRCC 的生物标志物和治疗靶点。