AUTHOR=Zhang Huaru , Qiu Xiaofu , Yang Guosheng 

TITLE=The CSRNP Gene Family Serves as a Prognostic Biomarker in Clear Cell Renal Cell Carcinoma

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.620126

DOI=10.3389/fonc.2021.620126

ISSN=2234-943X

ABSTRACT=<p>The cysteine-serine-rich nuclear protein (<italic>CSRNP</italic>) 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 <italic>CSRNP</italic> family for patients with ccRCC. Therefore, the gene expression profiling interactive analysis database was used to analyze the mRNA expression of <italic>CSRNP</italic> family members (<italic>CSRNPs</italic>) 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 <italic>CSRNPs</italic> were evaluated using Metascape. Associations between the <italic>CSRNP</italic> 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 <italic>CSRNP1</italic> and <italic>CSRNP3</italic> 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<sub>mRNA of</sub><italic><sub>CSRNP1</sub></italic> + 0.820 × exp<sub>mRNA of</sub><italic><sub>CSRNP2</sub></italic> − 1.428 × exp<sub>mRNA of</sub><italic><sub>CSRNP3</sub></italic>. 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 <italic>CSRNP</italic> with 28 types of immunocytes in tumor and normal tissues. A higher expression of <italic>CSRNP1</italic> and <italic>CSRNP3</italic> was associated with a better prognosis in both the high- and low-mutant burden groups. Cg19538674, cg07772537, and cg07811002 of <italic>CSRNP1</italic>, <italic>CSRNP2</italic>, and <italic>CSRNP3</italic>, respectively, were the predominant DNA methylation sites affecting OS. The <italic>CSRNP</italic> gene family signature may serve as a prognostic biomarker for predicting OS in patients with ccRCC. The association between <italic>CSRNPs</italic> and immune infiltration might offer future clinical treatment options.</p>