Abstract
BackgroundPatients with ovarian cancer represent a heterogeneous population with a variable prognosis and response to chemotherapy. Plasma DNA has been shown to have a prognostic value in different types of cancer including ovarian carcinoma. Whether total circulating DNA, which can be assessed much easier without knowing the tumor-specific mutations, has similar informative value is currently unknown. The aim of this study was to evaluate the prognostic value of extracellular DNA in advanced ovarian cancer.MethodsThis prospective study included 67 patients (pts) with ovarian cancer treated with 1st line paclitaxel and carboplatin (25 pts) and paclitaxel, carboplatin and bevacizumab (42 pts). Thirty-five patients had optimal surgical debulking before chemotherapy. Extracellular DNA was quantified using real time PCR before administration of chemotherapy (67 pts) and after 6 cycles of chemotherapy (44 pts).ResultsTotal extracellular DNA (ecDNA), as well as extracellular DNA of nuclear (nDNA) and mitochondrial origin (mtDNA) significantly (p < 0.05) decreased after 6 cycles of chemotherapy (by 54%, 63% and 52%, respectively. Patients with stage I disease had significantly lower mtDNA compared to patients with stage II-IV (8604 vs. 16, 984 ge/mL, p = 0.03). Patients with lower baseline nDNA had superior progression-free (HR = 0.35 (0.14–0.86)) and overall survival (HR = 0.18 (0.04–0.77). The prognostic value of nDNA was confirmed independent of tumor stage and confirmed in multivariate analysis.ConclusionsOur data suggest that ecDNA of both, nuclear and mitochondrial origin could be added to prognostic markers in ovarian cancer. Analysis of ecDNA does not require the knowledge of tumor-specific mutations in contrast to the quantification of tumor-derived ecDNA. Study of the dynamics and cell type-specific source of the ecDNA could shed light on its biology in cancer and might help to direct the treatment of ovarian cancer.
Highlights
Patients with ovarian cancer represent a heterogeneous population with a variable prognosis and response to chemotherapy
The study Gray et al analyzing extracellular DNA in metastatic melanoma patients showed that lower extracellular DNA levels prior to treatment significantly correlated with response to therapy and prolonged progression free survival, regardless to therapy type
We found that ovarian cancer patients with stage I disease had significantly lower mtDNA compared to patients with stage II-IV
Summary
Patients with ovarian cancer represent a heterogeneous population with a variable prognosis and response to chemotherapy. Plasma DNA has been shown to have a prognostic value in different types of cancer including ovarian carcinoma. Kalavska et al Journal of Ovarian Research (2018) 11:85 quantitative analysis of extracellular DNA as on novel non-invasive approach to follow patients after treatment, monitor therapeutic response and promote earlier detection of recurrences in different types of cancer including ovarian carcinoma [7, 8]. The study Gray et al analyzing extracellular DNA in metastatic melanoma patients showed that lower extracellular DNA levels prior to treatment significantly correlated with response to therapy and prolonged progression free survival, regardless to therapy type. Quantitative analysis of tumor associated mutant BRAF extracellular DNA revealed that higher overall response rate to BRAF inhibitors and longer progression free survival were seen in melanoma patients with lower concentration of basal mutant BRAF extracellular DNA [15, 16]. Fiegl et al measured RASSF1A DNA methylation of extracellular DNA in the serum to monitor response of women with breast cancer and presence of RASSF1A methylation 1 year after primary surgery was evaluated as an independent predictor of poor outcome in these patients [18]
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