Abstract
This study aimed at exploring the expression characteristics and functional roles of PTTG1 in ccRCC by bioinformatics analysis and in-vitro experiments. Differentially expressed genes were screened based on TCGA-KIRC and GSE168845 and the protein-protein interaction network was constructed. The risk regression model was constructed by Lasso regression and the key prognostic genes were obtained by combining immune infiltration and pathway enrichment analysis. Genes and proteins were quantified using RT-qPCR and western blot. MTT assay was used to detect the vitality of cells. Cell apoptosis and cell cycle were detected by flow cytometry. The comet assay was adopted to detect the damage degree of cell DNA. Six significant DDR-relevant prognostic genes (CCNA2, CDC45, CTLA4, FOXM1, PLK1, and PTTG1) were obtained. Immune infiltration results showed that CTLA4 was significantly positively correlated to T cells CD8. Besides, PTTG1 was negatively correlated to T cells CD4 memory resting, but remarkably positively correlated with both T cells CD8 and T cells regulatory. Compared with normal renal proximal tubular epithelial cells, the protein expression of PTTG1 was up-regulated at both mRNA and protein levels in ccRCC tissues. PTTG1could notably promote the proliferation of 786-O cells, and significantly inhibited apoptosis, cycle arrest and DNA damage of 786-O cells. PTTG1 may play a carcinogenic role by promoting the proliferation of ccRCC cells and inhibiting apoptosis. PTTG1 is expected to become a potential diagnostic and prognostic biomarker as well as an immunotherapy target for ccRCC.