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

BMC Cancer. 2020 May 24;20(1):467. doi: 10.1186/s12885-020-06965-4.


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-Drp1Ser637 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-Drp1Ser637 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-Drp1Ser637 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-Drp1Ser637 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.

Keywords: CaMKI; Drp1; Epithelial ovarian cancer; Phospho-Drp1Ser637; Prognostic biomarker.

MeSH terms

  • Adenocarcinoma, Clear Cell / metabolism
  • Adenocarcinoma, Clear Cell / pathology*
  • Adenocarcinoma, Clear Cell / therapy
  • Adenocarcinoma, Mucinous / metabolism
  • Adenocarcinoma, Mucinous / pathology*
  • Adenocarcinoma, Mucinous / therapy
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Combined Modality Therapy
  • Cystadenocarcinoma, Serous / metabolism
  • Cystadenocarcinoma, Serous / pathology*
  • Cystadenocarcinoma, Serous / therapy
  • Dynamins / metabolism*
  • Endometrial Neoplasms / metabolism
  • Endometrial Neoplasms / pathology*
  • Endometrial Neoplasms / therapy
  • Female
  • Follow-Up Studies
  • Humans
  • Middle Aged
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Ovarian Neoplasms / therapy
  • Prognosis
  • Retrospective Studies
  • Survival Rate


  • Biomarkers, Tumor
  • DNM1L protein, human
  • Dynamins