Growth Differentiation Factor-15 as a candidate biomarker in gynecologic malignancies: a meta-analysis

Introduction: Growth Differentiation Factor-15 (GDF-15) has emerged as a novel marker in gynecological cancers. But its suitability in clinical diagnostics is yet to be recognized. Materials and methods: We sorted out eligible studies from multiple online databases like Pubmed, Cochrane, ClinicalTrials.gov, Google Scholar, Web of Science, Embase, Scopus, LILACS, and Opengrey. The terms used were 'Growth Differentiation Factor-15', 'GDF-15', 'Macrophage Inhibitory Cytokine-1', 'MIC-1', 'Ovarian cancer', 'Ovarian carcinoma', 'Endometrial cancer', 'Endometrial carcinoma', 'Uterine cancer', 'Uterine Carcinoma', 'Cervical cancer', 'Cervical carcinoma', 'diagnosis', 'sensitivity', 'specificity', 'prognosis', and 'outcome'. Of the full-text, potentially eligible records, six were found eligible for inclusion into our meta-analysis. Studies were selected only if the diagnosis was proven by pathology, cases recruited were those without any prior treatment, sufficient diagnostic accuracy data were present for GDF-15 in gynecological cancers, and ethical approval was taken from Institutional Ethics Committee. Nonclinical research and animal studies were excluded. We took the assistance of the Rayyan QCRI software for the screening and selection process. We conducted the study following Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines and used Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) to assess the risk of bias. The protocol was registered at PROSPERO, registration number CRD42019130097. Results: We extracted diagnostic accuracy data from the articles and evaluated the role of GDF-15 by pooling the sensitivity, specificity, and diagnostic odds ratio (DOR) and plotting a summary receiver operating characteristic (SROC) curve. Since there was heterogeneity across the studies, the random-effects model was employed to carry out the integration. The meta-analysis showed that GDF-15 has a pooled DOR of 12.74 at 80.5% sensitivity and 74.1% specificity, with an area under the curve (AUC) of 0.84. Conclusion: Our analysis suggests that GDF-15 may be a useful candidate marker to differentiate malignant from non-malignant tumors of the female reproductive system.