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Dihydrofolate reductase as a predictor for poor response to platinum-based chemotherapy in epithelial ovarian cancer
Min Wang1, Ting Hu1, Ke-Yu Xie2
1Department of Obstetrics and Gynecology, Second People's Hospital of Chengdu Chengdu 610047, Sichuan, China.
Background:
Platinum-based chemotherapy is the first line chemotherapy regimen for ovarian cancer patients. However, chemotherapy resistance is observed in a large proportion of patients. It is urgently needed to investigate prognostic biomarkers for chemo-sensitivity in ovarian cancer.
Methods:
Dihydrofolate reductase (DHFR) expression was measured by immunohistochemical staining in 108 specimens, as well as DHFR mRNA variants with qRT-PCR assays. The correlation between DHFR expression and platinum-based chemotherapy response was analyzed. The prognostic significance of DHFR expression was evaluated in ovarian cancer.
Results:
Positive DHFR expression was observed in 48 specimens, which was correlated to chemotherapy resistance in ovarian cancer patients. Elevated DHFR2 mRNA expression, rather than DHFR1, was observed in chemotherapy resistant tumors. Positive DHFR expression was correlated with higher histologic grade in ovarian cancer (P = 0.014). Kaplan-Meier analysis indicated that DHFR positive expression predicted poor disease-free survival (DFS) (P = 0.040), but not overall survival (OS) of ovarian cancer patients (P = 0.706). The prognostic value was further supported by TCGA data analysis. Cox regression analysis indicated that positive DHFR expression was an independent detrimental factor for disease progression for ovarian cancer patients (P = 0.016).
Conclusion:
DHFR level measurement was a valuable prognostic biomarker for chemo-sensitivity of ovarian cancer. Molecular analysis for DHFR variants will provide important evidence for chemotherapy regimen options.
