Prognostic impact of Dynamin related protein 1 (Drp1) in epithelial ovarian cancer

Abstract

Background

The mitochondrial fission protein, Dynamin related protein 1 (Drp1), and its upstream protein calcium/calmodulin–dependent protein kinase I (CaMKI) play a critical role in chemoresistance in ovarian cancer (OVCA). Thus, we examined the expression of Drp1, CaMKI and their phosphorylated forms and their prognostic impact in epithelial OVCA patients.

Methods

Expression analysis was performed by immunohistochemistry (IHC) of paraffin-embedded tumor samples from 49 patients with epithelial OVCA. Staining intensity and the percentage of positively stained tumor cells were used to calculate an immunoreactive score (IRS) of 0–12. The expression scores calculated were correlated with clinicopathological parameters and patient survival.

Results

High immunoreactivity of phospho-Drp1 ^Ser637 was significantly correlated with high-grade serous carcinoma (HGSC) ( p = 0.034), residual postoperative tumor of > 1 cm ( p = 0.006), and non-responders to adjuvant chemotherapy ( p = 0.007), whereas high expression of CaMKI was significantly correlated with stage III/IV [International Federation of Gynecologists and Obstetricians (FIGO)] ( p = 0.011) and platinum-resistant recurrence ( p = 0.030). ROC curve analysis showed that Drp1, phospho-Drp1 ^Ser637 and CaMKI could significantly detect tumor progression with 0.710, 0.779, and 0.686 of area under the curve (AUC), respectively. The Kaplan-Meier survival curve showed that patients with high Drp1, phospho-Drp1 ^Ser637 and CaMKI levels had significantly poorer progression free survival (PFS) ( p = 0.003, p < 0.001 and p = 0.017, respectively). Using multivariate analyses, phospho-Drp1 ^Ser637 was significantly associated with PFS [ p = 0.043, hazard ratio (HR) 3.151, 95% confidence interval (CI) 1.039–9.561].

Conclusions

Drp1 and CaMKI are novel potential candidates for the detection and prognosis of epithelial OVCA and as such further studies should be performed to exploit their therapeutic significance.