title: Periostin in tumor microenvironment is associated with poor prognosis and platinum resistance in epithelial ovarian carcinoma.
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.
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan and School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Pi-Lin
authors.initials: PL
authors.lastname: Sung
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Jan
authors.affiliation: Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Lin
authors.affiliation: Department of Pathology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chao-Cheng
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Hao
authors.initials: H
authors.lastname: Lin
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan and School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kuo-Chang
authors.initials: KC
authors.lastname: Wen
authors.affiliation: Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan and School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Kuan-Chong
authors.initials: KC
authors.lastname: Chao
authors.affiliation: Department of Pathology, Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Chiung-Ru
authors.initials: CR
authors.lastname: Lai
authors.affiliation: Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan and School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Peng-Hui
authors.initials: PH
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan and School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chi-Mu
authors.initials: CM
authors.lastname: Chuang
authors.affiliation: Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan and School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hua-Hsi
authors.initials: HH
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan and School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Nae-Fang
authors.initials: NF
authors.lastname: Twu
authors.affiliation: Department of Obstetrics and Gynecology, Taipei Veterans General Hospital, Taipei, Taiwan and School of Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ming-Shyen
authors.initials: MS
authors.lastname: Yen
authors.affiliation: Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Michael
authors.initials: M
authors.lastname: Hsiao
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan.|Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chi-Ying F
authors.initials: CY
authors.lastname: Huang
mesh_terms: D018262:Adenocarcinoma, Clear Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D016889:Endometrial Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; D002945:Cisplatin
keywords: biomarker; epithelial ovarian cancer; microenvironment; periostin; platinum resistance