Introduction/Background Calretinin (CRT) is a calcium-binding protein, controlling intracellular calcium signaling. Besides its prominent expression in neurons, CRT has diagnostic implications in cancer, particularly in mesothelioma. In a recent liquid biopsy approach, plasma CRT level has been suggested for pre-diagnostic detection of mesothelioma. CRT is also expressed in serous ovarian cancer in about 23% of cases; however, clinical relevance of serum CRT is completely unknown and shall therefore be analyzed in the present study.
Methodology Serum calretinin (sCRT) was determined by CRT enzyme-linked immunoabsorbent assay (DLD-Diagnostika GmbH, Hamburg, Germany) in a total of 380 serum samples from 134 ovarian cancer patients (thereof n=115 (86%) with FIGO III or IV), including samples at primary diagnosis and at four follow-up reading points in the course of adjuvant treatment.
Results sCRT levels were significantly increased in ovarian cancer patients compared to healthy controls (ED=0.3 ng/ml, p<0.001) and enabled an accurate discrimination between cancer and controls (AUC=0.85). High sCRT levels at primary diagnosis correlated with platinum resistance (p=0.002), predicted suboptimal debulking surgery without achieving macroscopically complete tumor resection (p<0.001) and were associated with advanced FIGO-stage (p<0.001) and high volume of ascites (p<0.001). Increased sCRT levels at primary diagnosis were an independent predictor of poor PFS (HR=1.99, p=0.018) and indicated poor OS (HR=2.49, p=0.008). Higher sCRT levels before and after platinum-based chemotherapy were independent predictors of poor OS (HR=15.4, p=0.01; HR=5.59, p=0.026). Moreover, in the course of debulking surgery and adjuvant treatment, individual progression of sCRT levels provided independent prognostic information (OS: HR=7.38, p=0.034; PFS: HR=2.90, p=0.035) and additionally identified patients with poor prognosis.
Conclusion This is the first study, suggesting sCRT as an innovative liquid biopsy marker for the identification of ovarian cancer patients with primary platinum resistance and poor prognosis.
Disclosure Nothing to disclose.
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