Zhang Huaru, Qiu Xiaofu, Yang Guosheng
The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China.
Department of Urology, Guangdong Second Provincial General Hospital, Guangzhou, China.
Front Oncol. 2021 Mar 31;11:620126. doi: 10.3389/fonc.2021.620126. eCollection 2021.
The cysteine-serine-rich nuclear protein () family has prognostic value for various cancers. However, the association between this proteins and prognosis of clear cell renal cell carcinoma (ccRCC) remains unclear. This study aimed to determine the prognostic value of the family for patients with ccRCC. Therefore, the gene expression profiling interactive analysis database was used to analyze the mRNA expression of family members () in relation with survival. Combined and independent prognostic values of CSRNPs were evaluated using SurvExpress and multivariate Cox regression analyses, respectively. Potential signaling pathways impacted by were evaluated using Metascape. Associations between the family and immunocyte infiltration were determined from single-sample gene set enrichment analysis. Both cBioPortal and MethSurv were used to explore whether genomic and epidemic alterations might influence prognosis. We found that when both and had a low expression, patients with ccRCC had a worse overall survival (OS). Therefore, a prognostic signature was constructed as follows: risk score = -0.224 × exp + 0.820 × exp - 1.428 × exp . We found that OS was worse in patients from the high- than from the low-risk groups (AUC = 0.69). Moreover, this signature was an independent predictor after adjusting for clinical features. Functional enrichment analysis positively associated CSRNPs with the acute inflammatory response and humoral immune response pathways. This was validated by correlating each with 28 types of immunocytes in tumor and normal tissues. A higher expression of and was associated with a better prognosis in both the high- and low-mutant burden groups. Cg19538674, cg07772537, and cg07811002 of , , and , respectively, were the predominant DNA methylation sites affecting OS. The gene family signature may serve as a prognostic biomarker for predicting OS in patients with ccRCC. The association between and immune infiltration might offer future clinical treatment options.
富含半胱氨酸和丝氨酸的核蛋白()家族对多种癌症具有预后价值。然而,该蛋白与透明细胞肾细胞癌(ccRCC)预后之间的关联仍不清楚。本研究旨在确定该家族对ccRCC患者的预后价值。因此,利用基因表达谱交互分析数据库分析该家族成员()的mRNA表达与生存的关系。分别使用SurvExpress和多变量Cox回归分析评估CSRNPs的联合和独立预后价值。使用Metascape评估受影响的潜在信号通路。从单样本基因集富集分析确定该家族与免疫细胞浸润之间的关联。使用cBioPortal和MethSurv来探究基因组和表观遗传改变是否可能影响预后。我们发现,当和均低表达时,ccRCC患者的总生存期(OS)较差。因此,构建了如下预后特征:风险评分 = -0.224 × exp + 0.820 × exp - 1.428 × exp 。我们发现,高风险组患者的OS比低风险组更差(AUC = 0.69)。此外,在调整临床特征后,该特征是一个独立的预测因子。功能富集分析将CSRNPs与急性炎症反应和体液免疫反应通路呈正相关。通过将每个与肿瘤和正常组织中的28种免疫细胞相关联来验证这一点。在高突变负荷组和低突变负荷组中,和的较高表达均与较好的预后相关。、和的Cg19538674、cg07772537和cg07811002分别是影响OS的主要DNA甲基化位点。该基因家族特征可能作为预测ccRCC患者OS的预后生物标志物。与免疫浸润之间的关联可能为未来的临床治疗提供选择。