Comprehensive molecular analyses and experimental validation of CDCAs with potential implications in kidney renal papillary cell carcinoma prognosis

Abstract

Previous reports have revealed that the abnormal expression of the cell division cycle-associated gene family (CDCAs) is closely associated with some human cancers. However, the precise functional roles and mechanisms of CDCAs in kidney renal papillary cell carcinoma (KIRP) remain unclear. In this study, RNA sequencing data from the Cancer Genome Atlas database and Genotype-Tissue Expression databases were utilized to perform the expression, correlation, survival, mutation, functional enrichment analysis, and immunoinfiltration analyses of CDCAs in KIRP. We found that the expression levels of CDCA genes were significantly increased in KIRP across multiple databases, as confirmed by immunohistochemistry and quantitative reverse transcription PCR (RT-qPCR). Moreover, increased expression of CDCA genes is significantly associated with poor prognosis. Univariate and multivariate Cox regression analyses demonstrated that pathologic T and N staging, NUF2, CDCA2, CDCA3, CDCA5, CBX2, CDCA7, and CDCA8 were independent prognostic factors for patients with KIRP. Utilizing these nine variables, we developed a nomogram prognostic model. Furthermore, the results of GO and KEGG functional enrichment analyses suggested that CDCA genes were associated with nuclear division, mitotic nuclear division, and chromosome segregation and were involved in the cell cycle, p53 signaling pathway, and cellular senescence. We found that the expression of NUF2, CDCA2, CDCA5, and CBX2 was closely associated with the expression of lymphocytes, immunostimulatory molecules, immunoinhibitory molecules, and chemokines. In summary, NUF2, CDCA2, CDCA3, CDCA5, CBX2, CDCA7, and CDCA8 are potential biomarkers for KIRP diagnosis and prognosis.

Keywords

• CDCA gene family
• Prognostic biomarkers
• Kidney renal papillary cell carcinoma