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

Abstract

The cysteine-serine-rich nuclear protein (CSRNP) 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 CSRNP family for patients with ccRCC. Therefore, the gene expression profiling interactive analysis database was used to analyze the mRNA expression of CSRNP family members (CSRNPs) 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 CSRNPs were evaluated using Metascape. Associations between the CSRNP 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 CSRNP1 and CSRNP3 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 × expmRNA ofCSRNP1 + 0.820 × expmRNA ofCSRNP2 − 1.428 × expmRNA ofCSRNP3. 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 CSRNP with 28 types of immunocytes in tumor and normal tissues. A higher expression of CSRNP1 and CSRNP3 was associated with a better prognosis in both the high- and low-mutant burden groups. Cg19538674, cg07772537, and cg07811002 of CSRNP1, CSRNP2, and CSRNP3, respectively, were the predominant DNA methylation sites affecting OS. The CSRNP gene family signature may serve as a prognostic biomarker for predicting OS in patients with ccRCC. The association between CSRNPs and immune infiltration might offer future clinical treatment options.

Integrated bioinformatics analysis of the NEDD4 family reveals a prognostic value of NEDD4L in clear-cell renal cell cancer

“…In order to show the reliability of our risk model, we compared it with other ccRCC risk models, and the results showed that our risk model has better prediction ability (Fig. S5) (Zhang, Qiu & Yang, 2021;Fei, Chen & Xu, 2021;Chu et al, 2021;Xing et al, 2021). Based on the complementary perspective of the corresponding tumor, the model provides a personalized score for individual patients and a valuable new prognostic evaluation method for clinicians.…”

Peer Review #1 of "Integrated bioinformatics analysis of the NEDD4 family reveals a prognostic value of NEDD4L in clear-cell renal cell cancer (v0.1)"

“…The ROC analysis of the TCGA testing dataset showed that the AUC was 0.76 at 1 year, 0.69 at 3 years, and 0.68 at 5 years (Figure 6E), while that of the TCGA entire dataset showed that the AUC was 0.74 at 1 year, 0.71 at 3 years, and 0.74 at 5 years (Figure 6F). As reflected by the AUC values at 1 year, 3 year and 5 years, the signatures developed in our work had relatively better performance in predicting outcome of ccRCC patients (Figure 6F, Supplementary Figure 5) (Zhang et al, 2021;Fei et al, 2021;Chu et al, 2021;Xing et al, 2021b).…”

Identification and comprehensive analysis of circRNA–miRNA–mRNA regulatory networks in osteoarthritis

“…MiR-30c has also recently been considered as a suppressor of bone gamma-carboxyglutamate protein ( BGLAP ) in osteogenesis ( 50 ). Target DEGs of miR-30c in our analysis were mostly related to the anti-apoptosis of abnormal tumor cells, including MAP3K9 in lung cancer ( 46 ), ST6GALNAC5 in prostate cancer ( 51 ), CSRNP3 in clear renal cell carcinoma ( 52 ), ZNF703 in breast tumors ( 53 ), and CLSPN in brain tumors ( 54 ). Thus, upregulation of hsa_circ_0102564 might help reveal the downstream mechanism involved in the abnormal maturation and proliferation of chondrocytes in OA.…”