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.Funding Information This study was funded by Medical Faculty of Military Medical Academy, University of Defense, Serbia [grant MFVMA/02/20–22], and Ministry of Education, Science and Technological Development of the Republic of Serbia [grant #172035, #III41026