Decreased mitochondrial SIRT3 expression is a potential molecular biomarker associated with poor outcome in breast cancer

作者：Desouki Mohamed Mokhtar; Doubinskaia Irina; Gius David; Abdulkadir Sarki A^*

来源：Human Pathology, 2014, 45(5): 1071-1077.

DOI：10.1016/j.humpath.2014.01.004

• Sirt3
• Breast cancer
• Clinical outcomes
• Sirtuins
• Metabolism
• Mitochondria

SIRT3 is a genomically expressed, mitochondrial localized tumor suppressor protein where it directs multiple metabolic processes by deacetylating downstream protein substrates. Genetic deletion of Sirt3 in mice leads to the spontaneous development of mammary tumors starting at 1 year, and decreased SIRT3 messenger RNA has been observed in several human tumors including breast malignancies. In this investigation, we assessed SIRT3 expression in human breast cancer tissue microarray and examined the relationship between SERT3 expression and outcome in patients with breast cancer. SIRT3 protein expression is significantly lower in neoplastic compared with normal breast epithelium, including normal epithelium adjacent to tumors. Patients with breast cancer in the lowest quartile of SIRT3 expression had a significantly shorter locoregional relapse-free survival (hazard ratio, 0.53 [0.47-0.61]; log-rank P = 0). Notably, low SIRT3 expression was associated with reduced locoregional relapse-free survival in all breast cancer subtypes analyzed, including ER+, ER-, HER2+, and basal subtypes (hazard ratios, 0.44-0.65; log-rank P = 0-.0019). These results highlight the importance of the SERT3 as a tumor suppressor protein in breast cancer and suggest that SIRT3 may be a potential molecular biomarker to identify high-risk patients across all molecular subtypes of breast cancer.

• 出版日期2014-5
• 单位西北大学