Objective: This study investigated the relationship between 13 proteins involved in DNA damage and the outcomes of patients with recurrent ovarian cancer (ROC).
Patients and methods: Immunohistochemistry staining was performed in 114 diagnostic samples from patients with serous ROC who participated in the OVA-301 study, which compared pegylated liposomal doxorubicin (PLD) with a combination of trabectedin plus PLD. Percentage of positive cells for every marker was calculated and correlated with overall response rate (ORR), progression-free survival (PFS) and overall survival (OS).
Results: A statistically significant correlation between high levels of nibrin and lower ORR (P=0.03), shorter PFS (P=0.007) and shorter OS (P=0.01) was observed. After stratification, in patients with platinum-sensitive disease treated with the combination of trabectedin plus PLD, high levels of nibrin correlated with lower ORR (P=0.01) and shorter PFS (P=0.02). A better clinical outcome (ORR, PFS and OS) was also associated to low levels of CHK2 in trabectedin plus PLD treated patients. No correlations were found in PLD-treated patients. According to the results of a multivariate analysis, there was a statistically significant correlation between high nibrin (P=0.001) and low BRCA2 levels (P=0.03) and a worse PFS, and between high nibrin levels and a worse OS (P=0.006).
Conclusion: Our results indicate that high nibrin expression seems to be associated with a worse clinical outcome in serous ROC, particularly in patients treated with the combination trabectedin plus PLD. Prospective studies to determine clinical usefulness of nibrin as a possible biomarker in other series of patients with ROC are warranted.
Keywords: Molecular marker; Nibrin; Ovarian cancer; Trabectedin.
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