title: Tumor stress-induced phosphoprotein1 (STIP1) as a prognostic biomarker in ovarian cancer.
abstract: Stress-induced phosphoprotein 1 (STIP1) has been recently identified as a released biomarker in human ovarian cancer. In addition, STIP1 secreted by human ovarian cancer cells has been shown to promote tumor cell proliferation by binding to ALK2 (activin A receptor, type II-like kinase 2) and activating the SMAD-ID3 signaling pathways. In this study, a total of 330 ovarian cancer tumor samples were evaluated for STIP1 expression by immunohistochemistry and analyzed for a possible correlation with patient characteristics and survival. The quantification of immunoreactivity was accomplished by applying an immunohistochemical scoring system (histoscore). Patients with high-level STIP1 expression (histoscore ≥169) had a significantly worse survival (high STIP1, mean survival time = 76 months; low STIP1, mean survival time = 112 months; P<0.0001). Moreover, STIP1 histoscores were significantly higher in high-grade tumors (grade 3) than in low-grade (grade 1-2) malignancies (P<0.0001), suggesting that STIP1 may be a proxy for tumor aggressiveness. The results of multivariable analysis revealed that high STIP1 histoscores, advanced stages, histologic types, and the presence of residual disease (≥2 cm) were independent predictors of poor prognosis. The addition of STIP1 histoscores improved the prediction of overall and progression-free survival rates in the multivariable Cox proportional hazard model. The treatment of ovarian cancer cells with recombinant STIP1 stimulated cell proliferation and migration, but co-treatment with anti-STIP1 antibodies abrogated this effect. Our findings suggest that STIP1 expression may be related to prognosis and that the STIP1 pathway may represent a novel therapeutic target for human ovarian cancer.
authors.affiliation: Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan. angel945@cgmh.org.tw
authors.forename: Angel
authors.initials: A
authors.lastname: Chao
authors.forename: Chyong-Huey
authors.initials: CH
authors.lastname: Lai
authors.forename: Chia-Lung
authors.initials: CL
authors.lastname: Tsai
authors.forename: Swei
authors.initials: S
authors.lastname: Hsueh
authors.forename: Chuen
authors.initials: C
authors.lastname: Hsueh
authors.forename: Chiao-Yun
authors.initials: CY
authors.lastname: Lin
authors.forename: Hung-Hsueh
authors.initials: HH
authors.lastname: Chou
authors.forename: Yu-Jr
authors.initials: YJ
authors.lastname: Lin
authors.forename: Hsi-Wen
authors.initials: HW
authors.lastname: Chen
authors.forename: Ting-Chang
authors.initials: TC
authors.lastname: Chang
authors.forename: Tzu-Hao
authors.initials: TH
authors.lastname: Wang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D006360:Heat-Shock Proteins; C079373:STIP1 protein, human