Reduced HMGCR Expression in Clear Cell Renal Cell Carcinoma Is Associated With Poor Patient Prognosis.

Abstract

Background/aim: Renal cell carcinoma (RCC) is a heterogeneous malignancy, with clear cell renal cell carcinoma (KIRC) being the most common subtype, characterized by von Hippel-Lindau (VHL) tumor suppressor gene inactivation and hypoxia-inducible factor (HIF) pathway activation, leading to enhanced angiogenesis and tumor progression. Although targeted therapies are available, the prognosis remains poor. Statins targeting HMG-CoA reductase (HMGCR) may influence RCC outcomes; however, the findings are inconsistent and subtype-specific effects are unclear. Although high HMGCR expression is associated with improved overall survival in KIRC, its relationship with disease-free survival in other RCC subtypes remains unknown. This study analyzed HMGCR expression and its prognostic significance in KIRC, papillary renal cell carcinoma (KIRP), and chromophobe renal cell carcinoma (KICH) using TCGA data.

Materials and methods: We analyzed HMGCR mRNA expression and survival in patients with KIRC, KIRP, and KICH using the TCGA database with the GEPIA2, UALCAN and UCSC Xena platforms.

Results: Decreased expression levels of HMGCR were significantly associated with shorter overall and disease-free survival in patients with KIRC. In contrast, no significant differences in overall survival or disease-free survival were observed in patients with KIRP or KICH. Furthermore, multivariable Cox proportional hazards analysis identified HMGCR as an independent prognostic factor in KIRC.

Conclusion: Our results suggest that low HMGCR expression may be a poor prognostic factor in patients with KIRC.