High MUC16 gene expression levels as a potential prognostic and predictive marker in ovarian cancer

Introduction. The development of chemoresistance is a key factor limiting the efficacy of ovarian cancer therapy. Although high MUC16 gene expression levels in tumors are a known adverse prognostic factor, its role in predicting response to specific chemotherapeutic agents remains understudied. This led to the hypothesis that the adverse prognostic value of MUC16 expression levels may be mediated by its contribution to the development of chemoresistance.

Aim. To evaluate the association between MUC16 gene expression levels and in vitro resistance to standard chemotherapy agents, including carboplatin, cisplatin, and paclitaxel, as well as key clinicopathological characteristics (BRCA1/2 mutation status, platinum sensitivity) and progression-free survival in patients with ovarian carcinoma.

Materials and methods. Tumor samples were obtained from 35 patients with ovarian malignancies, predominantly high-grade serous carcinoma. MUC16 gene expression levels were determined using quantitative real-time polymerase chain reaction. Tumor cell chemoresistance was assessed in vitro in primary cultures using a resazurin metabolic assay, followed by the calculation of the resistance index (Resistance Sensitivity Index, RSI) for each drug. Statistical analysis was performed using Spearman’s rank correlation analysis, the Mann–Whitney U test, and the log-rank test.

Results. High MUC16 gene expression levels were associated with shortened progression-free survival (p = 0.0437). A statistically significant positive correlation was identified between MUC16 gene expression levels and the paclitaxel RSI (R = 0.3614; p = 0.0388). However, no associations were found with the RSI for platinum-based drugs. Furthermore, no relationship was established between MUC16 gene expression levels and BRCA1/2 mutation status (p = 0.8180) or the platinum sensitivity/resistance status of the tumors (p = 0.2899).

Conclusion. High MUC16 gene expression levels are associated with reduced progression-free survival and paclitaxel resistance, suggesting its potential as an unfavorable prognostic and predictive marker. Thus, determining MUC16 gene expression levels prior to therapy may have clinical potential for disease prognosis and for identifying patients for whom taxane-based treatment will likely be ineffective.