Decreased sirtuin 4 expression is associated with poor prognosis in patients with invasive breast cancer.

Abstract

Aberrant metabolism is a hallmark of human cancer. Glutamine metabolism has been identified as a central metabolic pathway in cancer and thus, targeting glutamine metabolism may exhibit therapeutic potential. Sirtuin 4 (SIRT4) is an important molecule that mediates the blockade of glutamine catabolism by inhibiting glutamate dehydrogenase. In the present study, SIRT4 protein expression levels were analyzed in 409 breast cancer tissues and 241 paired adjacent non-cancerous tissues by immunohistochemical analysis and the correlation between SIRT4 expression and the clinicopathological features was evaluated. SIRT4 protein was markedly increased in the breast cancer cells compared with adjacent non-tumor mammary cells and was correlated with estrogen receptor, progesterone receptor, nuclear-associated antigen Ki-67 and tumor protein p53 status, as well as breast cancer subtypes. Furthermore, low SIRT4 expression was associated with poor overall survival in breast cancers patients, particularly in Luminal A patients. Univariate and multivariate analyses confirmed that increased SIRT4 expression was an independent predictive factor of good prognosis for breast cancer patients. In conclusion, SIRT4 expression represents a significant favorable prognostic factor for patients with invasive breast cancer.