PuSH - Publication Server of Helmholtz Zentrum München: Plasmin(Ogen) serves as a favorable biomarker for prediction of survival in advanced high-grade serous ovarian cancer.

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Zhao, S.* ; Dorn, J.* ; Napieralski, R.* ; Walch, A.K. ; Diersch, S.* ; Kotzsch, M.* ; Ahmed, N.* ; Hooper, J.* ; Kiechle, M.* ; Schmitt, M.* ; Magdolen, V.*

Plasmin(Ogen) serves as a favorable biomarker for prediction of survival in advanced high-grade serous ovarian cancer.

Biol. Chem. 398, 765-773 (2017)

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n 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 antitumorigenic 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. 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.

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