Hachim Ibrahim Y, Hachim Mahmood Y, López-Ozuna Vanessa M, Ali Suhad, Lebrun Jean-Jacques
Division of Hematology, Cancer Research Program, Research Institute of the McGill University Health Centre, McGill University Montreal, Quebec H4A 3J1, Canada.
Division of Medical Oncology, Department of Medicine, Cancer Research Program, Research Institute of the McGill University Health Centre, McGill University Montreal, Quebec H4A 3J1, Canada.
Hum Pathol. 2016 Nov;57:140-151. doi: 10.1016/j.humpath.2016.07.002. Epub 2016 Jul 19.
The transforming growth factor-β (TGFβ) plays a dual role in breast cancer, acting as a tumor suppressor in early carcinomas while promoting tumor metastasis in more advanced breast carcinoma. As a result, the prognostic role of TGFβ and its signaling components in breast cancer remains unclear. Here we evaluated the expression levels of TGFβ signaling receptors TβRII and TβRI using human breast cancer tissue microarrays and a large publicly available gene profiling database in relation to various clinicopathological parameters. Our results indicate that breast cancer tissues express lower TβRII and TβRI protein levels compared with normal breast tissue. In contrast to TβRI expression, TβRII mRNA expression levels were also significantly downregulated in invasive breast cancer compared with normal breast tissue (4.18-fold downregulation, P=9.3×10). Interestingly, within the cancer cases analyzed, our results revealed a direct correlation between high TβRII and TβRI expression levels and classic poor prognostic clinicopathological parameters, including larger tumor size, advanced tumor stage, and poorly differentiated tumors. Next, we examined TGFβ receptors' expression in relation to breast cancer molecular subtypes. Importantly, our results revealed that whereas expression of TGFβ receptors in luminal A and triple-negative breast cancer showed no correlation with patient outcome, their expression in luminal B and HER2 subtypes showed significant association with favorable patient outcome. Together, these results indicate that although TGFβ receptors are downregulated in breast cancer, their expression in tumors is an indicator of aggressive breast cancer phenotype. Moreover, the relation between TGFβ pathway and patient outcome is breast cancer subtype dependent.
转化生长因子-β（TGFβ）在乳腺癌中发挥双重作用，在早期癌中作为肿瘤抑制因子，而在更晚期的乳腺癌中促进肿瘤转移。因此，TGFβ及其信号传导成分在乳腺癌中的预后作用仍不清楚。在这里，我们使用人乳腺癌组织芯片和一个大型公开可用的基因谱数据库，评估了TGFβ信号受体TβRII和TβRI的表达水平，并将其与各种临床病理参数相关联。我们的结果表明，与正常乳腺组织相比，乳腺癌组织中TβRII和TβRI蛋白水平较低。与TβRI表达相反，与正常乳腺组织相比，浸润性乳腺癌中TβRII mRNA表达水平也显著下调（下调4.18倍，P = 9.3×10）。有趣的是，在分析的癌症病例中，我们的结果显示高TβRII和TβRI表达水平与经典的不良预后临床病理参数之间存在直接相关性，包括更大的肿瘤大小、晚期肿瘤分期和低分化肿瘤。接下来，我们研究了TGFβ受体的表达与乳腺癌分子亚型的关系。重要的是，我们的结果显示，虽然TGFβ受体在腔面A型和三阴性乳腺癌中的表达与患者预后无关，但它们在腔面B型和HER2亚型中的表达与患者良好预后显著相关。总之，这些结果表明，尽管TGFβ受体在乳腺癌中下调，但其在肿瘤中的表达是侵袭性乳腺癌表型的一个指标。此外，TGFβ通路与患者预后之间的关系取决于乳腺癌亚型。
