Prognostic significance of two lipid metabolism enzymes, HADHA and ACAT2, in clear cell renal cell carcinoma

Renal cell carcinoma (RCC) is one of the leading causes of cancer mortality in adults, but there is still no acknowledged biomarker for its prognostic evaluation. Our previous proteomic data had demonstrated the dysregulation of some lipid metabolism enzymes in clear cell RCC (ccRCC). In the present study, we elucidated the expression of two lipid metabolism enzymes, hydroxyl-coenzyme A dehydrogenase, alpha subunit (HADHA) and acetyl-coenzyme A acetyltransferase 2 (ACAT2), using Western blotting analysis, then assessed the prognostic potential of HADHA and ACAT2 using immunohistochemistry (IHC) on a tissue microarray of 145 ccRCC tissues. HADHA and ACAT2 were downregulated in ccRCC (P < 0.05); further IHC analysis revealed that HADHA expression was significantly associated with tumor grade, stage, size, metastasis, and cancer-specific survival (P = 0.004, P < 0.001, P < 0.001, P = 0.049, P < 0.001, respectively) and ACAT2 expression was significantly associated with tumor stage, size, and cancer-specific survival (P < 0.001, P = 0.001, P < 0.001, respectively). In addition, a strong correlation was found between HADHA and ACAT2 expression (R = 0.655, P < 0.001). Further univariate survival analysis demonstrated that high stage, big tumor size, metastasis, and HADHA and ACAT2 down-expression were associated with poorer prognosis on cancer-specific survival (P = 0.007, P = 0.005, P = 0.006, P < 0.001, P = 0.001, respectively), and multivariate analysis revealed that HADHA, stage, and metastasis were identified as independent prognostic factors for cancer-specific survival in patients with ccRCC (P = 0.018, P = 0.046, P = 0.001, respectively). Collectively, these findings indicated that HADHA could serve as a promising prognostic marker in ccRCC, which indicated lipid metabolism abnormality might be involved in ccRCC tumorigenesis.