The Diagnostic and Prognostic Values of HOXA Gene Family in Kidney Clear Cell Renal Cell Carcinoma

Abstract

Kidney renal clear cell carcinoma (KIRC) is one of the most common cancers with high mortality worldwide. As members of the homeobox (HOX) family, homeobox-A (HOXA) genes have been reported to play an increasingly important role in tumorigenesis and the progression of multiple cancers. However, limited studies have investigated the potential diagnostic and prognostic roles of HOXA genes in KIRC. In this research, we explored the expression pattern of the HOXA gene family in KIRC progression by differential analysis of expression profiles from The Cancer Genome Atlas (TCGA). By using univariate Cox analysis and lasso regression analysis, we comprehensively evaluated the prognostic value of HOXA genes and eventually identified a prognostic risk model consisting of five HOXA genes (HOXA2, HOXA3, HOXA7, HOXA11, and HOXA13). The risk model was further validated as a novel independent prognostic factor for KIRC patients based on the calculated risk score by Kaplan-Meier analysis, univariate and multivariate Cox regression analyses, and time-dependent receiver operating characteristic (ROC) curve analysis. Moreover, to explore the potential mechanism of tumorigenesis and clinical application of KIRC, we also developed the HOXA-based competing endogenous RNA (ceRNA) regulatory network and machine learning classification model. Valproic acid and tretinoin were predicted to be the most promising small molecules to adjuvant treatment of KIRC by mining the CMAP and DGIdb drug database. Subsequently, pathway and functional enrichment analyses provided us with new ways to search for a possible mechanism of action of drugs. Taken together, our study demonstrated the nonnegligible role of HOXA genes in KIRC and constructed an effective prognostic and diagnostic model, which offers novel insights into KIRC prognosis.