Integrated Transcriptome Analysis of Radioresistant Cells Revealed Genes and Pathways Predictive Of Tumor Response to Radiotherapy and Chemotherapy in Breast Cancer

• Published in: Advanced therapeutics Vol. 7; no. 7
• Main Authors: Perez‐Añorve, Isidro X., Flores‐Fortis, Mauricio, Patiño‐Morales, Carlos C., Ortiz‐Gutierrez, Elizabeth, Del Moral‐Hernandez, Oscar, Gonzalez‐De la Rosa, Claudia H., Soto‐Reyes, Ernesto, Bonilla‐Moreno, Raul, Chavez Saldaña, Margarita, Landero‐Huerta, Daniel A., Ortega‐Bernal, Daniel, Villegas, Nicolas, Arechaga‐Ocampo, Elena
• Format: Journal Article
• Language: English
• Published: 01.07.2024
• Subjects: breast cancer; chemosensitivity; hub‐genes; radioresistance; transcriptome
• ISSN: 2366-3987; 2366-3987
• DOI: 10.1002/adtp.202300274

Breast cancer cells exposed to radiotherapy frequently develop radiation resistance through molecular and phenotypic changes. While there is evidences of pathways controlling radioresistance, the evolution of diverse cell phenotypes and transcriptional changes as mediators of radioresistance in breast cancer are restricted. Moreover, the effectiveness of the chemotherapy on radioresistant cells remains uncertain. In this work, an isogenic model of radioresistant breast cancer cells (RR cells) is used to study this phenotype. RR cells show high survival rates after radiation, moreover, RR cells of the triple negative breast cancer (TNBC) subtype show a significantly advanced invasiveness phenotype. Notably, RR cells are significantly sensitive to chemotherapy by inhibit cell survival and promote apoptosis. Transcriptomics and gene co‐expression network analysis identify differentially expressed genes (DEGs) and hub genes related to survival and apoptosis pathways in the RR cells of luminal subtype, while in TNBC subtype, cell migration, cell differentiation, and immune pathways are enriched. Hub genes predict the failure of radiotherapy in breast cancer patients, but they are also related to pathological complete response after chemotherapy. Transcriptome changes during acquired radioresistance uncover genes and pathways associated to radio and chemotherapy response. These results demonstrate that radioresistant pathways may converge to develop collateral chemo‐sensitivity. Breast cancer develops radioresistance through molecular and phenotypic changes related to transcriptional reprogramming. Differential gene expression analysis and gene co‐expression networks uncover key genes related to cell survival and apoptosis in radioresistant luminal breast tumors, while cell migration, cell differentiation, and immune genes are enriched in radioresistant TNBC. All these pathways converge to develop collateral chemo‐sensitivity.