Comparison of the Expression Levels of Senescence Genes between Human Normal Kidney Cells and Kidney Tumor Cells According to Age

Background: Although most carcinogenic mutations induce senescence, senescence-induced cell-cycle arrest can prevent mutations, resulting in the suppression of tumorigenesis. On the contrary, the senescence-associated secretory phenotype also contributes to a pro-inflammatory and growth-stimulatory microenvironment that can promote tumor development. Despite their potential correlation, the relationship between tumor- and aging-related transcriptional changes is largely unknown. Methods: We integrated three datasets in publicly available bulk and single-cell RNA-seq: Gene Expression Omibus (GSE207493, GSE159115, GSE131685), and applied new senescent gene set in CellAge and SenMayo to our dataset. We classified them into younger and older age groups to compare senescent gene expression patterns in normal kidney and kidney tumor cells based on the age. The study aims to investigate the differences in expression patterns of senescence genes between them. Results: We clustered normal kidney and kidney tumor cells in the UMAP plot. Kidney tumor was located on the proximal tubule. We compared senescent gene expression levels between normal kidney and kidney tumor cells, focusing on differences between younger and older age groups. ACTB and GAPDH were in the control group, and the expression of representative senescent genes p21 (CDKN1A), p16 (CDKN2A), and p53 (TP53) was confirmed. Among them, the expression difference in CDKN1A was found to be greater in kidney tumor cells than in normal kidney cells. I applied the new senescent gene set, and CTSS, G0S2, S100A11, NEAT1, and SERPINA1 showed similar patterns. This suggests that in kidney tumors, the difference in expression of senescent genes becomes greater with older age. Conclusion: Kidney tumorigenesis might be associated with senescent genes. This result can serve as a basis for future studies on the role of aging and senescence in human kidney malignancies. Funding: Government Support – Non-U.S.The difference of senescent gene expression between younger and older age in normal kidney cells and kidney tumor cells