Hypoxia-induced autophagy in triple negative breast cancer: association with prognostic variables, patients’ survival and response to neoadjuvant chemotherapy

• Published in: Virchows Archiv : an international journal of pathology 2023-05, Vol.482 (5), p.823-837
• Main Authors: El-Guindy, Dina M., Ibrahim, Fatma MKh, Ali, Dina A., El-Horany, Hemat El-Sayed, Sabry, Nesreen M., Elkholy, Rasha A., Mansour, Wael, Helal, Duaa S.
• Format: Article
• Language: English
• Subjects: Autophagy; Bcl-2 protein; Beclin-1; Breast cancer; Cell survival; Chemotherapy; Gene expression; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Hypoxia-inducible factor 1a; Immunohistochemistry; Medical prognosis; Medicine; Medicine & Public Health; Metastases; Metastasis; MicroRNAs - genetics; Neoadjuvant Therapy; Original; Original Article; Pathology; Prognosis; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Reverse transcription; Survival; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - pathology; Tumor Microenvironment; Tumors
• ISSN: 0945-6317; 1432-2307
• DOI: 10.1007/s00428-023-03527-4

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.