Expression of SIRT1 , SIRT3 and SIRT6 Genes for Predicting Survival in Triple-Negative and Hormone Receptor-Positive Subtypes of Breast Cancer

Triple-negative breast cancer (TNBC) is characterized by aggressive phenotype and a poorer prognosis compared to the estrogen and progesterone receptor positive, Her2 negative (ER + PR + Her2-) breast cancer. Increasing evidence suggests that sirtuins, a family of histone deacetylases, could have an important role in aggressiveness of TNBC’s. The current study evaluated the potential clinical relevance of SIRT1 , SIRT3 and SIRT6 gene expressions in two prognostically distinctive subtypes of breast cancer, the most aggressive TNBC and the least aggressive ER + PR + Her2- tumors. Total RNAs were isolated from 48 TNBC and 63 ER + PR + Her2- tumor samples. Relative gene expression was determined by SYBR Green RT-PCR and delta-delta Ct method, normalized to GAPDH . Mean gene expression of both SIRT1 and SIRT3 was significantly lower in the TNBC compared to ER + PR + Her2- tumors ( p = 0.0001). Low SIRT1 and SIRT6 expressions associated with worse overall survival in ER + PR + Her2- patients ( p = 0.039, p = 0.006, respectively), while TNBC patients with high SIRT1 tend to have a poor prognosis ( p = 0.057). In contrast, high expression of SIRT3 in TNBC patients associated with higher histological grade ( p = 0.027) and worse overall survival ( p = 0.039). The Cox regression analysis revealed that low SIRT1 expression could be an independent prognostic marker of poor survival in ER + PR + Her2- breast cancers (HR = 11.765, 95% CI:1.234–100, p = 0.033). Observed differential expression of SIRT1 , SIRT3 and SIRT6 genes in TNBC and ER + PR + Her2- subtypes, with opposite effects on patients’ survival, suggests context-dependent mechanisms underlying aggressiveness of breast cancer. Further investigations are necessary to evaluate sirtuins as potential biomarkers and therapeutic targets in breast cancer.