The Prognostic and Therapeutic Implications of the Chemoresistance Gene BIRC5 in Triple-Negative Breast Cancer

SIMPLE SUMMARY: TNBC is the most aggressive type of breast cancer affecting women worldwide, and chemoresistance poses a significant clinical challenge associated with a poor prognosis. The molecular mechanisms causing this treatment resistance in TNBC patients have not been extensively studied. This study was designed to find a prognostic biomarker that can accurately predict the patient’s disease status. We discovered that the chemoresistance gene BIRC5 could be a potential therapeutic target and a useful predictive biomarker for TNBC patients. We examined the expression of the genes that BIRC5 targets. Differentially expressed target genes were associated with carcinogenesis, tumor suppression, and cancer development. The most significant target genes were tumor oncogenes (TK1, KIF2C, UBE2C, AURKB) and tumor suppressors (CALCOCO1, CIRBP, KLHDC1, CBX7). It was concluded from this study that the findings might offer novel insights into TNBC chemoresistance and pinpoint key therapeutic targets, thereby assisting clinicians in developing alternative treatment options for TNBC patients. ABSTRACT: Chemoresistance affects TNBC patient treatment responses. Therefore, identifying the chemoresistant gene provides a new approach to understanding chemoresistance in TNBC. BIRC5 was examined in the current study as a tool for predicting the prognosis of TNBC patients and assisting in developing alternative therapies using online database tools. According to the examined studies, BIRC5 was highly expressed in 45 to 90% of TNBC patients. BIRC5 is not only abundantly expressed but also contributes to resistance to chemotherapy, anti-HER2 therapy, and radiotherapy. Patients with increased expression of BIRC5 had a median survival of 31.2 months compared to 85.8 months in low-expression counterparts (HR, 1.73; CI, 1.4–2.13; p = 2.5 × 10(−7)). The overall survival, disease-free survival, relapse-free survival, distant metastasis-free survival, and the complete pathological response of TNBC patients with high expression of BIRC5 who received any chemotherapy (Taxane, Ixabepilone, FAC, CMF, FEC, Anthracycline) and anti-HER2 therapy (Trastuzumab, Lapatinib) did not differ significantly from those patients receiving any other treatment. Data obtained indicate that the BIRC5 promoter region was substantially methylated, and hypermethylation was associated with higher BIRC5 mRNA expression (p < 0.05). The findings of this study outline the role of BIRC5 in chemotherapy-induced resistance of TNBC, further indicating that BIRC5 may serve as a promising prognostic biomarker that contributes to chemoresistance and could be a possible therapeutic target. Meanwhile, several in vitro studies show that flavonoids were highly effective in inhibiting BIRC5 in genetically diverse TNBC cells. Therefore, flavonoids would be a promising strategy for preventing and treating TNBC patients with the BIRC5 molecule.