Upregulated Expression of Calcium-Dependent Annexin A6: A Potential Biomarker of Ovarian Carcinoma.

PURPOSE:An early and accurate diagnosis of ovarian carcinoma (OC) may reduce morbidity and mortality of the patients. To improve the clinical outcome in OC patients, the present study is aimed at identifying robust biomarkers for early OC diagnosis. EXPERIMENTAL DESIGN: In order to look for early-stage protein markers, a systematic protein profiling approach involving 2-dimensional electrophoresis coupled with mass spectrometric analyses of human malignant and non-malignant ovarian biopsy samples, is performed. RESULTS:Six 2D gel spots, corresponding to five proteins, display statistically significant differential expression in the tumor tissues compared to benign controls (FDR ≤ 0.05; PMF score ≥ 79). Ingenuity pathway analysis predicts two proteins, that is, Ca²⁺ -dependent membrane-binding protein annexin A6 (AnxA6) and the metabolic enzyme l-lactate dehydrogenase A chain, as potential predictive biomarkers. Increased expression of AnxA6 is further ascertained by Western blot and enzyme linked immunosorbent assay in the resected tissues and the plasma samples. The expression is found markedly increasing particularly in the advanced stage tumors. CONCLUSIONS AND CLINICAL RELEVANCE:The significant upregulation of AnxA6 in OC, reported for the first time, is likely to provide insight into the mechanism of OC progression, which may lead to the design of potential diagnostic and therapeutic strategies.

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