Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
Clinical Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.
Virchows Arch. 2023 May;482(5):823-837. doi: 10.1007/s00428-023-03527-4. Epub 2023 Mar 20.
Autophagy is a cellular response to diverse stresses within tumor microenvironment (TME) such as hypoxia. It enhances cell survival and triggers resistance to therapy. This study investigated the prognostic importance of HIF-1α and miR-210 in triple negative breast cancer (TNBC). Also, we studied the relation between beclin-1 and Bcl-2 and their prognostic relevance in triple negative breast cancer. Furthermore, the involvement of hypoxia-related markers, beclin-1 and Bcl-2 in mediating resistance to neoadjuvant chemotherapy (NACT) in TNBC was evaluated. Immunohistochemistry was performed to evaluate HIF-1α, beclin-1 and Bcl-2 expression whereas, miR-210 mRNA was detected by quantitative reverse transcription PCR (q-PCR) in 60 TNBC patients. High HIF-1α expression was related to larger tumors, grade III cases, positive lymphovascular invasion, advanced stage, high Ki-67 and poor overall survival (OS). High miR-210 and negative Bcl-2 expression were related to nodal metastasis, advanced stage and poor OS. High beclin-1 was associated with grade III, nodal metastasis, advanced stage and poor OS. Also, high beclin-1 and negative Bcl-2 were significantly associated with high HIF-1α and high miR-210. High HIF- 1α, miR-210 and beclin-1 as well as negative Bcl-2 were inversely related to pathologic complete response following NACT. High beclin-1 and lack of Bcl-2 are significantly related to hypoxic TME in TNBC. High HIF-1α, miR-210, and beclin-1 expression together with lack of Bcl-2 are significantly associated with poor prognosis as well as poor response to NACT. HIF-1α and miR-210 could accurately predict response to NACT in TNBC.
自噬是肿瘤微环境（TME）中多种应激的细胞反应，如缺氧。它增强细胞存活并引发对治疗的抵抗。本研究调查了 HIF-1α 和 miR-210 在三阴性乳腺癌（TNBC）中的预后重要性。此外，我们还研究了 beclin-1 和 Bcl-2 之间的关系及其在三阴性乳腺癌中的预后相关性。此外，还评估了缺氧相关标志物 beclin-1 和 Bcl-2 在介导 TNBC 对新辅助化疗（NACT）的耐药性中的作用。通过免疫组织化学评估 HIF-1α、beclin-1 和 Bcl-2 的表达，而通过定量逆转录 PCR（q-PCR）检测 60 例 TNBC 患者的 miR-210 mRNA。高 HIF-1α 表达与肿瘤较大、III 级病例、阳性淋巴管浸润、晚期、高 Ki-67 和总体生存（OS）不良相关。高 miR-210 和阴性 Bcl-2 表达与淋巴结转移、晚期和 OS 不良相关。高 beclin-1 与 III 级、淋巴结转移、晚期和 OS 不良相关。此外，高 beclin-1 和阴性 Bcl-2 与高 HIF-1α 和高 miR-210 显著相关。高 HIF-1α、miR-210 和 beclin-1 以及阴性 Bcl-2 与 NACT 后病理完全缓解呈负相关。高 beclin-1 和缺乏 Bcl-2 与 TNBC 缺氧 TME 显著相关。高 HIF-1α、miR-210 和 beclin-1 表达以及缺乏 Bcl-2 与预后不良以及对 NACT 的反应不良显著相关。HIF-1α 和 miR-210 可准确预测 TNBC 对 NACT 的反应。
