Identification of biomarkers for the diagnosis and targets for therapy in patients with clear cell ovarian cancer: a systematic literature review.

Clear cell ovarian cancer (CCOC) is a rare type of epithelial cancer often resistant to platinum-based chemotherapy. Biomarkers for the diagnosis of CCOC, and targets for immunotherapy, both have the potential to improve outcomes for patients. Our review aims to determine whether any antigens already identified in the literature could fulfil this remit. PubMed, Medline, Web of Science, Scopus, Cochrane, CINAHL and EMBASE were searched and included all reported studies up until August 2021. Primary research articles on human adult females including at least 10 CCOC patients were included. Quality assurance was carried out using a modified version of the QUADAS-2 tool. Sensitivity, specificity and area under the curve were extracted from each included study by two independent reviewers. Twenty-three articles were included which identified 19 gene transcripts/proteins and one antibody, with reported sensitivities between 21% and 100% and specificities between 0% and 100% for expression in CCOC and differentiation from other epithelial ovarian cancer subtypes, benign gynaecological disease or normal tissue. Twelve studies identified biomarkers with a sensitivity and specificity above 80%. A panel of biomarkers consisting of IMP3, napsin A and hepatocyte nuclear factor 1 beta achieved the highest area under the curve of 0.954. This review demonstrates that there are promising candidate biomarkers for the diagnosis of CCOC, some of which are highly specific, and have the potential to act as targets for therapy. However, larger cohort studies are needed to validate these biomarkers and their potential use in clinical practice.