Background
Clear cell renal carcinoma (ccRCC) seriously threatens people’s health worldwide. Numerous studies have revealed that histone deacetylases (HDACs) affect the cell proliferation, apoptosis and cell differentiation. Nevertheless, the biological function of histone deacetylation modification related genes in the carcinogenesis, progression, and prognosis of ccRCC remains poorly understood.
Method
Bulk transcriptomic data and clinical information of ccRCC patients were obtained from the TCGA database and the Chinese PLA General Hospital. A total of 36 histone deacetylation genes were included in our study. Univariate cox regression analysis, least absolute shrinkage and selection operator (LASSO) regression, random forest (RF) analysis, and protein-protein interaction (PPI) network analysis were employed to identify key genes affecting the prognosis of ccRCC patients. The ‘oncoPredict’ algorithm was utilized for drug-sensitive analysis. GSEA and KEGG enrichment analysis was used to explore the potential biological function. The ssGSEA algorithm was used for tumor immune microenvironment analysis. The expression levels of HDAC10 were validated by RT-PCR and immunohistochemistry (IHC). EdU assay, CCK-8 assay, cell transwell migration and invasion assay and colony formation assay were performed to detect the proliferation and invasion ability of ccRCC cells. A nomogram incorporating HDAC10 and clinicopathological characteristics was established to predict the prognosis of ccRCC patients.
Result
Two machine learning algorithms and PPI analysis identified four histone deacetylation genes that have a significant association with the prognosis of ccRCC patients, with HDAC10 being the key gene among them. HDAC10 is highly expressed in ccRCC and its high expression is associated with poor prognosis. Pathway enrichment and the experiments of 5-ethynyl-2′-deoxyuridine (EdU) staining, CCK-8 assay, cell transwell migration and invasion assay and colony formation assay detected that HDAC10 may mediated the proliferation and the metastasis of ccRCC. HDAC10 may also be involved in reshaping the tumor microenvironment (TME) of ccRCC. A clinically reliable prognostic predictive model was established by incorporating HDAC10 and other clinicopathological characteristics ( https://nomogramhdac10.shinyapps.io/HDAC10_Nomogram/ ).
Conclusion
Our study found the increased expression of HDAC10 was closely associated with poor prognosis of ccRCC patients. HDAC10 may have a pro-tumorigenic effect on ccRCC and promote the proliferation and metastasis of ccRCC, which may provide new light on targeted therapy for ccRCC.