Characterizing excision repair cross-complementing family genes as drug resistance biomarkers in breast cancer

Abstract

Abstract Background Excision repair cross-complementing (ERCC) genes are important regulators of DNA repair processes, the aberrant expression of which may lead to treatment failures of breast cancer. The prognostic significance of the ERCC genes in several cancers has been investigated, except for breast cancer; therefore, we explored the ERCC genes, including ERCC1, ERCC2, ERCC3, ERCC4, ERCC5, ERCC6, and ERCC8 in breast cancer, particularly during drug resistance processes. Results Using the 2021 provisional study of The Metastatic Breast Cancer Project from cBioPortal, we identified ERCC genetic alterations in 8–36% of patients, where most alterations were considered amplifications followed by deep deletions. Pathway enrichment analyses identified Wnt signaling enrichment which contributed to cell proliferation. ERCC2 had the highest epigenetic alteration levels at 7 DNA methylation sites. Also, the mRNA levels of ERCC1, ERCC2, ERCC4, ERCC6, and ERCC8 were higher in patients with breast cancer when compared to normal breast tissues, with higher ERCC2 but lower ERCC8 levels in metastatic breast tissues. Breast cancer patients with low ERCC6 levels had better overall survival rates than the groups with higher ERCC6 levels. ERCC1, ERCC2, and ERCC4 were identified as endocrine therapy response predictors. ERCC1 was specifically an antihuman epidermal growth factor receptor therapy predictor, and ERCC1, ERCC2, ERCC6, and ERCC8 were chemotherapy response predictors. Conclusion We used bioinformatics to investigate and identify the roles of ERCC genes in breast cancer resistant cells, in particular ERCC1, ERCC2, and ERCC6. We also showed how the Wnt pathway and DNA repair processes had a role in drug resistance in breast cancer cells, but further studies are required to validate those results.