title: Plasmin(ogen) serves as a favorable biomarker for prediction of survival in advanced high-grade serous ovarian cancer.
abstract: In serous ovarian cancer, the clinical relevance of tumor cell-expressed plasmin(ogen) (PLG) has not yet been evaluated. Due to its proteolytic activity, plasmin supports tumorigenesis, however, angiostatin(-like) fragments, derived from PLG, can also function as potent anti-tumorigenic factors. In the present study, we assessed PLG protein expression in 103 cases of advanced high-grade serous ovarian cancer (FIGO III/IV) by immunohistochemistry (IHC). In 70/103 cases, positive staining of tumor cells was observed. In univariate Cox regression analysis, PLG staining was positively associated with prolonged overall survival (OS) [hazard ratio (HR)=0.59, p=0.026] of the patients. In multivariable analysis, PLG, together with residual tumor mass, remained a statistically significant independent prognostic marker (HR=0.49, p=0.009). In another small patient cohort (n=29), we assessed mRNA expression levels of PLG by quantitative PCR. Here, elevated PLG mRNA levels were also significantly associated with prolonged OS of patients (Kaplan-Meier analysis; p=0.001). This finding was validated by in silico analysis of a microarray data set (n=398) from The Cancer Genome Atlas (Kaplan-Meier analysis; p=0.031). In summary, these data indicate that elevated PLG expression represents a favorable prognostic biomarker in advanced (FIGO III/IV) high-grade serous ovarian cancer.
authors.affiliation: .
authors.forename: Shuo
authors.initials: S
authors.lastname: Zhao
authors.affiliation: .
authors.forename: Julia
authors.initials: J
authors.lastname: Dorn
authors.affiliation: .
authors.forename: Rudolf
authors.initials: R
authors.lastname: Napieralski
authors.affiliation: .
authors.forename: Axel
authors.initials: A
authors.lastname: Walch
authors.affiliation: .
authors.forename: Sandra
authors.initials: S
authors.lastname: Diersch
authors.affiliation: .
authors.forename: Matthias
authors.initials: M
authors.lastname: Kotzsch
authors.affiliation: .
authors.forename: Nancy
authors.initials: N
authors.lastname: Ahmed
authors.affiliation: .
authors.forename: John D
authors.initials: JD
authors.lastname: Hooper
authors.affiliation: .
authors.forename: Marion
authors.initials: M
authors.lastname: Kiechle
authors.affiliation: .
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmitt
authors.affiliation: .
authors.forename: Viktor
authors.initials: V
authors.lastname: Magdolen
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010958:Plasminogen / Q000235:genetics / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies; D016019:Survival Analysis; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D010958:Plasminogen; D014568:Urokinase-Type Plasminogen Activator
keywords: PAI-1; immunohistochemistry; ovarian cancer; plasmin; plasminogen; quantitative PCR; uPA