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.

与雌激素和孕激素受体阳性，Her2阴性（ER + PR + Her2-）乳腺癌相比，三阴性乳腺癌（TNBC）的特征在于具有侵略性的表型，预后较差。越来越多的证据表明，sirtuins是一种组蛋白脱乙酰基酶，可能在TNBC的侵袭性中起重要作用。本研究评估了SIRT1，SIRT3和SIRT6基因表达在两种预后不同的乳腺癌亚型中的潜在临床相关性，即最具侵袭性的TNBC和侵袭性最弱的ER + PR + Her2-肿瘤。从48个TNBC和63个ER + PR + Her2-肿瘤样品中分离出总RNA。相对基因表达通过SYBR Green RT-PCR和delta-delta Ct方法确定，标准化为GAPDH。与ER + PR + Her2-肿瘤相比，TNBC中SIRT1和SIRT3的平均基因表达均显着降低（p  = 0.0001）。SIRT1和SIRT6的低表达与ER + PR + Her2患者的总体生存较差有关（分别为p  = 0.039，p  = 0.006），而SIRT1高的TNBC患者的预后较差（p  = 0.057）。相比之下，TNBC患者中SIRT3的高表达与较高的组织学分级（p  = 0.027）和较差的总生存期（p = 0.039）。Cox回归分析显示，SIRT1低表达可能是ER + PR + Her2乳腺癌生存不良的独立预后标志物（HR = 11.765，95％CI：1.234–100，p  = 0.033）。在TNBC和ER + PR + Her2-亚型中观察到SIRT1，SIRT3和SIRT6基因的差异表达，对患者的生存有相反的影响，表明了乳腺癌侵袭性的背景依赖机制。进一步的研究是必要的，以评估沉默调节蛋白作为乳腺癌的潜在生物标志物和治疗靶标。