Serum calretinin as an independent predictor for platinum resistance and prognosis in ovarian cancer.

Abstract

Calretinin (CRT) is a calcium-binding protein that controls intracellular calcium signaling. Besides its prominent expression in neurons, serum CRT (sCRT) has recently been suggested as blood-based biomarker for prediagnostic mesothelioma detection. CRT is expressed in ovarian cancer tissues in up to 40% of cases; however, its clinical relevance as blood-based biomarker for ovarian cancer is unknown. sCRT was determined by calretinin enzyme-linked immunoabsorbent assay (Calretinin-ELISA, DLD Diagnostika GmbH, Hamburg, Germany) in a total of 515 serum samples from 116 healthy controls and 134 ovarian cancer patients (thereof 86% with Fédération Internationale de Gynécologie et d'Obstétrique [FIGO] III/IV), including samples at primary diagnosis and at four longitudinal follow-up time points in the course of treatment and at recurrence. sCRT level was significantly increased in ovarian cancer patients compared to healthy controls (estimated difference = 0.3 ng/ml, p < 0.001), was mostly independent from CA125 (r ≤ 0.388) and enabled accurate discrimination between cases and controls (area under the curve = 0.85). Higher sCRT level at primary diagnosis predicted suboptimal debulking (p < 0.001) and was associated with advanced FIGO-stage (p < 0.001) and increased amount of ascites (p < 0.001). sCRT levels at primary diagnosis and its dynamics in the course of chemotherapy were independent predictors for poor progression-free survival (hazard ratio [HR] = 1.99, confidence interval [CI] = [1.13-3.52], p = 0.0181) and overall survival (HR = 15.4, CI = [1.92-124], p = 0.0099). Furthermore, sCRT at primary diagnosis or a relative sCRT increase in the time interval between surgery and the onset of chemotherapy were both independent predictors of platinum resistance (OR = 4.99, CI = [3.50-16,001], p = 0.0016; OR = 2.41, CI = [1.37-6,026], p = 0.0271, respectively). This is the first study that suggests sCRT as liquid biopsy marker for independent prediction of platinum resistance and prognosis.