Quantitative assessment and clinical relevance of kallikrein-related peptidase 5 mRNA expression in advanced high-grade serous ovarian cancer

Background In 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 sta...

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Published in:BMC cancer Vol. 19; no. 1; pp. 696 - 9
Main Authors: Gong, Weiwei, Liu, Yueyang, Seidl, Christof, Diamandis, Eleftherios P., Kiechle, Marion, Drecoll, Enken, Kotzsch, Matthias, Magdolen, Viktor, Dorn, Julia
Format: Journal Article
Language:English
Published: London BioMed Central 15.07.2019
BioMed Central Ltd
BMC
Subjects:
Adult
Aged
Aged, 80 and over
Antigens
Ascites
Biomarkers
Biomarkers, Tumor - metabolism
Biomedical and Life Sciences
Biomedicine
Cancer Research
Carcinoma, Ovarian Epithelial - pathology
Chi-Square Distribution
Development and progression
Diagnosis
Enzyme-linked immunosorbent assay
Female
Gene expression
Genetic aspects
Genomes
Genomics
Health aspects
Health Promotion and Disease Prevention
Humans
Hydrolases
Kallikrein
Kallikreins - metabolism
Kaplan-Meier Estimate
KLK5
Medicine/Public Health
Messenger RNA
Middle Aged
mRNA expression
Neoplasm Staging
Oncology
Ovarian cancer
Ovarian Neoplasms - pathology
Polymerase chain reaction
Progression-Free Survival
Proportional Hazards Models
Proteases
Quantitative PCR
Real-Time Polymerase Chain Reaction
Regression analysis
Research Article
RNA
RNA, Messenger - genetics
Signaling peptides and proteins
Statistics, Nonparametric
Surgical Oncology
Tumors
Germany
KLK5
Quantitative PCR
Ovarian cancer
mRNA expression
ISSN:1471-2407, 1471-2407
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Abstract Background In 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. Methods We 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. Results A highly significant correlation between the mRNA expression levels and protein levels of KLK5 in tumor tissues was observed (r s  = 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). Conclusions These 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.
AbstractList Background In 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. Methods We 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. Results A highly significant correlation between the mRNA expression levels and protein levels of KLK5 in tumor tissues was observed (r.sub.s = 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 ([less than or equai to]500 ml vs. > 500 ml), remained an independent indicator for both OS and PFS (p < 0.001, p = 0.005, respectively). Conclusions These 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. Keywords: KLK5, Ovarian cancer, Quantitative PCR, mRNA expression
In 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. We 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. A highly significant correlation between the mRNA expression levels and protein levels of KLK5 in tumor tissues was observed (r.sub.s = 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 ([less than or equai to]500 ml vs. > 500 ml), remained an independent indicator for both OS and PFS (p < 0.001, p = 0.005, respectively). These 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.
In 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.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.We 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.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.A 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).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).These 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.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.
Abstract Background In 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. Methods We 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. Results A 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). Conclusions These 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.
Background In 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. Methods We 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. Results A highly significant correlation between the mRNA expression levels and protein levels of KLK5 in tumor tissues was observed (r s  = 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). Conclusions These 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.
In 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. We 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. A highly significant correlation between the mRNA expression levels and protein levels of KLK5 in tumor tissues was observed (r  = 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). These 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.
ArticleNumber 696
Audience Academic
Author Gong, Weiwei
Liu, Yueyang
Kiechle, Marion
Dorn, Julia
Drecoll, Enken
Diamandis, Eleftherios P.
Kotzsch, Matthias
Seidl, Christof
Magdolen, Viktor
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Issue 1
Keywords KLK5
Quantitative PCR
Ovarian cancer
mRNA expression
Language English
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Snippet Background In ovarian cancer, dysregulation of mRNA expression of several components of the family of the kallikrein-related peptidases (KLKs) is observed. In...
In ovarian cancer, dysregulation of mRNA expression of several components of the family of the kallikrein-related peptidases (KLKs) is observed. In this study,...
Background In ovarian cancer, dysregulation of mRNA expression of several components of the family of the kallikrein-related peptidases (KLKs) is observed. In...
Abstract Background In ovarian cancer, dysregulation of mRNA expression of several components of the family of the kallikrein-related peptidases (KLKs) is...
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StartPage 696
SubjectTerms Adult
Aged
Aged, 80 and over
Antigens
Ascites
Biomarkers
Biomarkers, Tumor - metabolism
Biomedical and Life Sciences
Biomedicine
Cancer Research
Carcinoma, Ovarian Epithelial - pathology
Chi-Square Distribution
Development and progression
Diagnosis
Enzyme-linked immunosorbent assay
Female
Gene expression
Genetic aspects
Genomes
Genomics
Health aspects
Health Promotion and Disease Prevention
Humans
Hydrolases
Kallikrein
Kallikreins - metabolism
Kaplan-Meier Estimate
KLK5
Medicine/Public Health
Messenger RNA
Middle Aged
mRNA expression
Neoplasm Staging
Oncology
Ovarian cancer
Ovarian Neoplasms - pathology
Polymerase chain reaction
Progression-Free Survival
Proportional Hazards Models
Proteases
Quantitative PCR
Real-Time Polymerase Chain Reaction
Regression analysis
Research Article
RNA
RNA, Messenger - genetics
Signaling peptides and proteins
Statistics, Nonparametric
Surgical Oncology
Tumors
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Title Quantitative assessment and clinical relevance of kallikrein-related peptidase 5 mRNA expression in advanced high-grade serous ovarian cancer
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