Identification of a signature of histone modifiers in kidney renal clear cell carcinoma

Abstract

Kidney renal clear cell carcinoma (KIRC) is a cancer that is closely associated with epigenetic alterations, and histone modifiers (HMs) are closely related to epigenetic regulation. Therefore, this study aimed to comprehensively explore the function and prognostic value of HMs-based signature in KIRC. HMs were first obtained from top journal. Then, the mRNA expression profiles and clinical information in KIRC samples were downloaded from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) datasets. Cox regression analysis and least absolute shrinkage and selection operator (Lasso) analysis were implemented to find prognosis-related HMs and construct a risk model related to the prognosis in KIRC. Kaplan-Meier analysis was used to determine prognostic differences between high- and low-risk groups. Immune infiltration and drug sensitivity analysis were also performed between high- and low-risk groups. Eventually, 8 HMs were successfully identified for the construction of a risk model in KIRC. The results of the correlation analysis between risk signature and the prognosis showed HMs-based signature has good prognostic value in KIRC. Results of immune analysis of risk models showed there were significant differences in the level of immune cell infiltration and expression of immune checkpoints between high- and low-risk groups. The results of the drug sensitivity analysis showed that the high-risk group was more sensitive to several chemotherapeutic agents such as Sunitinib, Tipifarnib, Nilotinib and Bosutinib than the low-risk group. In conclusion, we successfully constructed HMs-based prognostic signature that can predict the prognosis of KIRC.