Acetyl-CoA synthetase 2 enhances tumorigenesis and is indicative of a poor prognosis for patients with renal cell carcinoma.

Background: Acetyl-CoA synthetase 2 (ACSS2) is highly expressed in various cancers, whereas ACSS2 expression and function in renal cell carcinoma (RCC) are unknown.

Methods: We investigated ACSS2 expression in 198 human RCC tissues using immunohistochemistry, and analyzed its clinicopathological correlation and prognostic relevance. Overexpression and knockdown of ACSS2 were used to investigate the proliferation, migration and invasion of human RCC 786-O, 769-P, and ACHN cell lines.

Results: High-ACSS2 expression was associated with advanced T stage (P = 0.008), advanced tumor-node-metastasis stage (P = 0.015) and high University of California, Los Angeles, Integrated Staging System score category (P = 0.009). Multivariate analysis identified high-ACSS2 expression as a poor prognostic factor for recurrence-free survival (hazard ratio [HR] = 1.83, P = 0.038) and overall survival (HR = 1.60, P = 0.043). Cell-based functional assays showed that ACSS2 knockdown inhibited RCC cell growth, migration, and invasion, whereas overexpression of ACSS2 enhanced these effects. ACSS2 silencing inhibited PI3K/AKT signaling pathway.

Conclusion: ACSS2 may increase tumor progression and aggressive behavior and be an independent prognostic factor in RCC.