Prognostic Values of COL4As Transcriptional Expressions in Clear Cell Renal Cell Carcinoma Patients.

ABSTRACT

OBJECTIVE: The COL4A family genes (COL4As) are a set of extracellular matrix-related genes that have been proved a tight relationship among various cancers. However, the functional role of different COL4As (COL4A1/2/3/4/5/6) in clear cell renal cell carcinoma (ccRCC) is unclear. METHODS: We obtained the data from online open-access databases including ONCOMINE, UALCAN, GEPIA, Cancer Genome Atlas (TCGA), cBioPortal, METASCAPE, STRING, TIMER, GSCALite, MEXPRESS, and TISIDB to explore the correlation between COL4As expression and genome-wide difference, progression, prognosis, genetic mutation, functional enrichment, tumor immune microenvironment, and methylation in ccRCC patients. RESULTS: The significantly higher COL4A1/2 expression and lower COL4A3/4/5/6 expression were observed in ccRCC tissues than in normal kidney tissues. Transcriptomic levels of COL4A1/2/3/4 were significantly correlated with tumor grade and stage. The higher expression levels of COL4A1/2/3/4 were accompanied by a longer overall survival time (OS); the higher expression levels of COL4A3/4 with lower expression levels of COL4A5 were associated with a longer disease-free time (DFS). Univariate/multivariate regression model analysis showed that COL4A4 could be a potential independent biomarker for ccRCC prognosis. And a high mutation rate (29%) of COL4As was observed in ccRCC patients. However, there were no relationships between mutation rates of COL4As and OS, DFS in ccRCC patients (p>0.05). Besides, we founded that the COL4As expressions were significant associated with the infiltration of the immune cells, tumor-infiltrating lymphocytes, three immunomodulators (immunoinhibitory, immunostimulator, MHC molecule), chemokines, and receptors. CONCLUSION: The results suggested that the transcript levels of COL4As could act as potential indicators for early disease progression. The expression of COL4A4 could contribute directly to disease prognosis. Besides, COL4A1/2/3/4 widely participated in tumor immunity. However, further studies are needed to confirm their clinical values in the ccRCC patients.