Abstract
The interplay between tumor microenvironment and cancer that causes chemoresistance remains unclear. By analyzing public available microarray datasets, we identified that periostin (POSTN) was overexpressed in cancer stroma in epithelial ovarian cancer (EOC) patients. Immunohistochemistry analysis showed overexpression of stromal POSTN is a powerful independent poor prognostic predictor for EOC patients. Furthermore, patients with high levels of stromal POSTN tend to have higher percentage of cisplatin resistance compared to those with low levels of stromal POSTN. Moreover, we found POSTN treatment can induce cisplatin resistant and activate AKT pathway in A2780 cells in vitro. Inhibition of AKT activity by AKT inhibitor MK-2206 abolished POSTN-induced AKT activation and cisplatin resistance in vitro. Taken together, we found high POSTN expression in cancer microenvironment is correlated with poor prognosis in EOC patients and associated with platinum resistance. The effect of POSTN in cancer stroma cells may activate AKT pathway in tumor and AKT inhibitor can be beneficial to augment the efficacy of existing cancer therapeutics.
Highlights
Epithelial ovarian cancer (EOC) is the third most common type of gynecologic cancer in the United States but a leading cause of gynecologic cancer deaths
Unsupervised hierarchical clustering of the microarray data found that the POSTN was overexpressed in cancer stroma (CS) along with other cytokines, growth factors and extracellular matrix (ECM) components compared to normal stroma (NS) (Figure 1A)
POSTN protein immunoreactivity observed in cancer stromal cells was found to be a predictive marker for platinum response and survival prognosis
Summary
Epithelial ovarian cancer (EOC) is the third most common type of gynecologic cancer in the United States but a leading cause of gynecologic cancer deaths. It is estimated that 21,980 new cases were diagnosed in 2014, with 14,270 deaths [1]. Aggressive surgical cytoreduction followed by standard platinum-taxene chemotherapy generally improved the survival rate of EOC patients, the 5-year survival rate remains dismal (~30%) [2]. Platinum-resistance, defined as relapse within 6 months, is one of the major causes for the low survival rate. It is a big challenge for successful treatment and a reference for deciding second-line treatments [3]. Predictive biomarkers for platinum-resistance in EOC patients are desperately needed
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