Larissa Dettmar1, Nancy Ahmed1, Matthias Kotzsch2, Sandra Diersch1, Rudolf Napieralski1,3, Dalila Darmoul4,5, Manfred Schmitt1,3, Wilko Weichert6, Marion Kiechle1, Julia Dorn1, Viktor Magdolen7. 1. Clinical Research Unit, Department of Obstetrics and Gynecology, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. 2. Medizinisches Labor Ostsachsen, Dresden, Germany. 3. Therawis Diagnostics, Munich, Germany. 4. Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Saint Louis, Paris, France. 5. Universite Paris Diderot, Sorbonne Paris Cite, UMRS-S976, Paris, France. 6. Institute of Pathology, Technische Universität München and German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany. 7. Clinical Research Unit, Department of Obstetrics and Gynecology, Technische Universität München, Ismaninger Str. 22, 81675, Munich, Germany. viktor.magdolen@tum.de.
Abstract
PURPOSE: Gene expression of a variety of the 15 members of the KLK serine protease family is dysregulated in ovarian cancer. We aimed at determining the clinical relevance of KLK13 and KLK14 mRNA expression in tumor tissues of a homogeneous patient cohort afflicted with advanced high-grade serous ovarian cancer (FIGO stage III/IV). METHODS: mRNA expression levels of KLK13 and KLK14 were assessed by quantitative PCR in tumor tissue of 91 patients and related with clinical factors and patients' outcome. RESULTS: There was no significant association of KLK13 and KLK14 mRNA expression with the clinical factors ascitic fluid volume or residual tumor mass. In univariate Cox regression analysis, elevated KLK13 mRNA levels were significantly linked with shorter progression-free (PFS; hazard ratio [HR] = 1.97, P = 0.020) and overall survival (OS; HR = 1.81, P = 0.041). High KLK14 mRNA levels were significantly associated with prolonged PFS (HR = 0.44, P = 0.017) and showed a trend towards significance for OS (HR = 0.55, P = 0.070). In multivariable analysis, including the factors age, residual tumor mass, ascitic fluid volume, KLK13, and KLK14, both KLKs, apart from residual tumor mass, remained statistically independent predictive markers: patients with high KLK13 mRNA expression levels displayed a more than twofold increase risk for shorter PFS (HR = 2.14, P = 0.020) as well as OS (HR = 2.05, P = 0.028), whereas elevated KLK14 mRNA values were found to be significant for both, prolonged PFS (HR = 0.36, P = 0.007) and OS (HR = 0.46, P = 0.037). CONCLUSION: These results indicate that in advanced high-grade serous ovarian cancer KLK13 may become proficient for tumor-supporting functions, whereas KLK14 may have adopted tumor-suppressing activity.
PURPOSE: Gene expression of a variety of the 15 members of the KLK serine protease family is dysregulated in ovarian cancer. We aimed at determining the clinical relevance of KLK13 and KLK14 mRNA expression in tumor tissues of a homogeneous patient cohort afflicted with advanced high-grade serous ovarian cancer (FIGO stage III/IV). METHODS: mRNA expression levels of KLK13 and KLK14 were assessed by quantitative PCR in tumor tissue of 91 patients and related with clinical factors and patients' outcome. RESULTS: There was no significant association of KLK13 and KLK14 mRNA expression with the clinical factors ascitic fluid volume or residual tumor mass. In univariate Cox regression analysis, elevated KLK13 mRNA levels were significantly linked with shorter progression-free (PFS; hazard ratio [HR] = 1.97, P = 0.020) and overall survival (OS; HR = 1.81, P = 0.041). High KLK14 mRNA levels were significantly associated with prolonged PFS (HR = 0.44, P = 0.017) and showed a trend towards significance for OS (HR = 0.55, P = 0.070). In multivariable analysis, including the factors age, residual tumor mass, ascitic fluid volume, KLK13, and KLK14, both KLKs, apart from residual tumor mass, remained statistically independent predictive markers: patients with high KLK13 mRNA expression levels displayed a more than twofold increase risk for shorter PFS (HR = 2.14, P = 0.020) as well as OS (HR = 2.05, P = 0.028), whereas elevated KLK14 mRNA values were found to be significant for both, prolonged PFS (HR = 0.36, P = 0.007) and OS (HR = 0.46, P = 0.037). CONCLUSION: These results indicate that in advanced high-grade serous ovarian cancerKLK13 may become proficient for tumor-supporting functions, whereas KLK14 may have adopted tumor-suppressing activity.
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