Abstract
BackgroundIn ovarian cancer, dysregulation of mRNA expression of several components of the family of the kallikrein-related peptidases (KLKs) is observed. In this study, we have analyzed the KLK5 mRNA expression pattern in tumor tissue of patients suffering from high-grade serous ovarian cancer stage FIGO III/IV. Moreover, we have correlated the KLK5 mRNA levels with clinical outcome.MethodsWe assessed the mRNA expression levels of KLK5 in tumor tissue of 138 patients using quantitative PCR (qPCR). The mRNA levels were correlated with KLK5 antigen tumor tissue levels measured by ELISA (available for 41 of the 138 patients), established clinical features as well as patients’ outcome, using Chi-square-tests, Mann-Whitney U-tests and Spearman rank calculations as well as Cox regression models, Kaplan-Meier survival analysis and the log-rank test.ResultsA highly significant correlation between the mRNA expression levels and protein levels of KLK5 in tumor tissues was observed (rs = 0.683, p < 0.001). In univariate Cox regression analysis, elevated KLK5 mRNA expression was remarkably associated with reduced progression-free survival (PFS; p = 0.047), but not with overall survival (OS). Association of KLK5 mRNA expression with PFS was validated in silico using The Cancer Genome Atlas. For this, Affymetrix-based mRNA data (n = 377) were analyzed applying the Kaplan-Meier Plotter tool (p = 0.027). In multivariable Cox analysis, KLK5 mRNA values revealed a trend towards statistical significance for PFS (p = 0.095), whereas residual tumor mass (0 mm vs. > 0 mm), but not ascites fluid volume (≤500 ml vs. > 500 ml), remained an independent indicator for both OS and PFS (p < 0.001, p = 0.005, respectively).ConclusionsThese results obtained with a homogenous patient group with all patients suffering from advanced high-grade serous ovarian cancer support previous results suggesting elevated KLK5 mRNA levels as an unfavorable marker in ovarian cancer.
Highlights
In ovarian cancer, dysregulation of mRNA expression of several components of the family of the kallikrein-related peptidases (KLKs) is observed
Quantification of KLK5 mRNA levels in tumor tissue samples of advanced high-grade serous ovarian cancer patients (FIGO III/IV) KLK5 mRNA expression was quantified by quantitative PCR (qPCR) in tissue samples of 138 patients
In summary, the study presented here demonstrates that, in univariate analysis, elevated expression of KLK5 mRNA is significantly related with shortened progression-free survival (PFS) of patients afflicted with advanced high-grade serous ovarian cancer (HGSOC)
Summary
Dysregulation of mRNA expression of several components of the family of the kallikrein-related peptidases (KLKs) is observed. We have analyzed the KLK5 mRNA expression pattern in tumor tissue of patients suffering from high-grade serous ovarian cancer stage FIGO III/IV. Ovarian cancer (OC) is the fifth common cause of cancer-related death [1]. Late detection of OC is due to the fact that early stage OC frequently does not cause any obvious or specific symptoms [4]. Accumulating reports demonstrated that KLKs, when overexpressed in malignant tissues, are detectable in serum and in effusion fluids, consistent with the fact that KLKs are secreted by epithelial/glandular cells [9, 10]. KLKs may serve as biomarkers in detection of primary cancer, clinical diagnosis, and prediction of the clinical outcome [5]
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