Annexin A3 Is a Potential Predictor of Platinum Resistance in Epithelial Ovarian Cancer Patients in a Prospective Cohort

Abstract

Epithelial ovarian cancer (EOC) is the leading cause of death among gynecological malignancies and is rarely cured in the recurrent setting, mainly because of progressive chemoresistance, especially platinum resistance. In our previous studies, the platinum-resistance-related protein, annexin A3, was selected by comparative proteomics. In this study, we detected serum annexin A3 levels using a self-developed chemiluminescence immunoassay kit in a prospective EOC patient cohort. We also evaluated the capacity of serum annexin A3 levels to predict platinum resistance. Serum annexin A3 levels in healthy women exhibited a similar normal distribution (Z=0.723, P=0.673), allowing determination of a normal cutoff level of 0.11-1.45 ng/mL. Of the 89 EOC patients, 21 were platinum resistant and 68 were platinum sensitive. Residual disease after primary surgery (p=0.004) and serum annexin A3 levels (p=0.036) were both independent factors associated with platinum resistance. The AUC was 0.733 (95% confidence interval (CI), 0.627-0.823). The optimal cutoff value for serum annexin A3 levels was 2.05 ng/mL. Multivariate logistic analysis showed that expression of annexin A3 as assessed by immunohistochemistry (P=0.005) and residual tumor size (P=0.000) had a significant influence on platinum resistance. The AUC of ROC curve of annexin A3 expression by immunohistochemistry was 0.664 (95% CI, 0.554-0.763) and the cut off value was “>=moderate scores”. In conclusion, we demonstrate that annexin A3 is a secreted protein that may be measured in the peripheral blood using a self-developed, chemiluminescence immunoassay kit. Serum annexin A3 levels may be a potential predictor of platinum resistance in epithelial ovarian cancer patients.

Role of BRCA Mutations in the Modulation of Response to Platinum Therapy

“…For instance, the C118T and C8092A polymorphisms in ERCC1 have been strongly correlated with objective response rate and overall survival ( 89 ). Similarly, the levels of annexin A3 in the peripheral blood may be a potential predictor for platinum resistance in ovarian cancer ( 90 ). Although molecular markers have the potential to predict therapy response, rigorous validation in large patient cohorts would truly bring out the benefits of such predictions.…”

Annexin A3 in sepsis: novel perspectives from an exploration of public transcriptome data

“…[38][39][40][41] More relevant to the sepsis profiling data presented and discussed here, mechanistic studies point to a role played by ANXA3 in promoting cancer growth and metastasis. [42][43][44][45] Notably, a recent study also reported benefits of anti-ANXA3 monoclonal antibodies in a preclinical mouse model of HCC. 45 Although ANXA3 expression in many cancer cells seems to correlate directly with the rate of cellular proliferation, 47,48 the underlying mechanism(s) are undefined.…”

Extracellular Vesicles in Cancer

“…Exosomal proteins can also represent important biomarkers for the evaluation of efficacy of therapies. Thus, annexin A3 can be employed for early detection of the resistance to platinum-based therapy in ovarian cancer patients [135,136].…”