Periostin in tumor microenvironment is associated with poor prognosis and platinum resistance in epithelial ovarian carcinoma
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Pi-Lin Sung1,2, Yi-Hua Jan3, Shih-Chieh Lin4, Chao-Cheng Huang5, Hao Lin6, Kuo-Chang Wen1,2, Kuan-Chong Chao2, Chiung-Ru Lai4, Peng-Hui Wang2, Chi-Mu Chuang2, Hua-Hsi Wu2, Nae-Fang Twu2, Ming-Shyen Yen2, Michael Hsiao3, Chi-Ying F. Huang1,7
1Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
2Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan and School of Medicine, National Yang-Ming University, Taipei, Taiwan
3Genomics Research Center, Academia Sinica, Taipei, Taiwan
4Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan
5Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
6Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
7Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan
Michael Hsiao, e-mail: [email protected]
Chi-Ying F. Huang, e-mail: [email protected]
Keywords: periostin, platinum resistance, biomarker, microenvironment, epithelial ovarian cancer
Received: May 14, 2015 Accepted: December 02, 2015 Published: December 21, 2015
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.
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