Searching for new biomarkers in ovarian cancer patients: Rationale and design of a retrospective study under the Mermaid III project

Abstract

Ovarian cancer is a silent killer and, due to late diagnosis, the primary cause of death amongst gynecological cancers, killing approximately 376 women annually in Denmark. The discovery of a specific and sensitive biomarker for ovarian cancer could improve early diagnosis, but also treatment, by predicting which patients will benefit from specific treatment strategies. The Mermaid III project is consisting of 3 parts including “Early detection, screening and long-term survival,” “Biomarkers and/or prognostic markers” and “The infection theory.” The present paper gives an overview of the part regarding biomarkers and/or prognostic markers, with a focus on rationale and design.The study described has 3 major branches: microRNAs, epigenetics and Next Generation Sequencing. Tissue and blood from ovarian cancer patients, already enrolled in the prospective ongoing pelvic mass cohort, will be examined. Relevant microRNAs and DNA methylation patterns will be investigated using array technology. Patient exomes will be fully sequenced, and identified genetic variations will be validated with Next Generation Sequencing. In all cases, data will be correlated with clinical information on the patient, in order to identify possible biomarkers.A thorough investigation of biomarkers in ovarian cancer, including large numbers of different markers, has never been done before. Besides from improving diagnosis and treatment, other outcomes could be markers for screening, knowledge of the molecular aspects of cancer and the discovery of new drugs. Moreover, biomarkers are a prerequisite for the development of precision medicine. This study will attack the ovarian cancer problem from several angles, thereby increasing the chance of successfully contributing to saving lives.

Identification and validation of potential prognostic and predictive miRNAs of epithelial ovarian cancer

“…Patients recruited for our training cohort were included from the Pelvic Mass study, elaborated in previous papers [ 15 , 16 ]. The Pelvic Mass study is a prospective ongoing clinical study initiated in 2004 at the Gynecological Clinic, Rigshospitalet, Copenhagen University Hospital, Denmark, with the overall purpose to identify diagnostic and prognostic factors for OC [ 17 ]. Clinical information on all patients is continuously updated in the Danish Gynecologic Cancer Database and tumor tissue is handled and stored by the Danish CancerBiobank [ 5 , 16 ].…”

Oncomine™ Comprehensive Assay v3 vs. Oncomine™ Comprehensive Assay Plus

“…A total of 50 tissue samples were retrospectively collected from a prospective cohort of OC patients [16,17]. Patients were registered in the Pelvic Mass study/GOVEC study, a prospective cohort initiated in September 2004.…”

Prognostic Evidence of the miRNA-Based Ovarian Cancer Signature MiROvaR in Independent Datasets

“…While a clinical-grade assay for the transcriptome-based classification of HGSOC histotype is ready for "the prime time" [2], the new knowledge derived by single cell sequencing approaches adds a further level of complexity that suggests a re-interpretation, and actually limits the efficacy of transcriptome-based discrete HGSOC subtyping [23]. We have shown the potential role of miRNAs in predicting disease progression [5,24], and the Prahm et al study [8] enabled us to test our MiROvaR model in a totally independently collected, handled and profiled EOC patient dataset, thus following the rules for biomarkers validation [25], and confirming MiROvaR reliability as a biomarker of EOC early relapse, regardless of their histotypes. A biomarker such as MiROvaR, based on a tumor's molecular characteristics at diagnosis, once validated also on liquid biopsy, might help in patients' selection before any therapeutic treatment.…”