scholarly journals Insights into impact of DNA copy number alteration and methylation on the proteogenomic landscape of human ovarian cancer via a multi-omics integrative analysis

2018 ◽  
Author(s):  
Xiaoyu Song ◽  
Jiayi Ji ◽  
Kevin J. Gleason ◽  
John A. Martignetti ◽  
Lin S. Chen ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Copy Number ◽  
Quantitative Traits ◽  
Integrative Analysis ◽  
Omics Data ◽  
Dna Copy Number ◽  
Expression Levels ◽  
Dna Methylations ◽  
Mrna Expression Levels

In this work, we propose iProFun, an integrative analysis tool to screen for Proteogenomic Functional traits perturbed by DNA copy number alterations (CNA) and DNA methylations. The goal is to characterize functional consequences of DNA copy number and methylation alterations in tumors and to facilitate screening for cancer drivers contributing to tumor initiation and progression. Specifically, we consider three functional molecular quantitative traits: mRNA expression levels, global protein abundances, and phosphoprotein abundances. We aim to identify those genes whose CNAs and/or DNA methylations have cis-associations with either some or all three types of molecular traits. In comparison with analyzing each molecular trait separately, the joint modeling of multi-omics data enjoys several benefits: iProFun experienced enhanced power for detecting significant cis-associations shared across different omics data types; and it also achieved better accuracy in inferring cis-associations unique to certain type(s) of molecular trait(s). For example, unique associations of CNA/methylations to global/phospho protein abundances may imply post-translational regulations. We applied iProFun to ovarian high-grade serous carcinoma tumor data from The Cancer Genome Atlas and Clinical Proteomic Tumor Analysis Consortium, and identified CNAs and methylations of 500 and 122 genes, respectively, affecting the cis-functional molecular quantitative traits of the corresponding genes. We observed substantial power gain via the joint analysis of iProFun. For example, iProFun identified 130 genes whose CNAs were associated with phosphoprotein abundances by leveraging mRNA expression levels and global protein abundances. By comparison, analyses based on phosphoprotein data alone identified none. A group of these 130 genes clustered in a small region on Chromosome 14q, harboring the known oncogene, AKT1. In addition, iProFun identified one gene, CANX, whose DNA methylation has a cis-association with its global protein abundances but not its mRNA expression levels. These and other genes identified by iProFun could serve as potential drug targets for ovarian cancer.

scholarly journals Prognostic value of kallikrein-related peptidase 7 (KLK7) mRNA expression in advanced high-grade serous ovarian cancer

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Weiwei Gong ◽  
Yueyang Liu ◽  
Eleftherios P. Diamandis ◽  
Marion Kiechle ◽  
Holger Bronger ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Mrna Expression ◽  
Protein Level ◽  
Multivariate Analyses ◽  
Expression Patterns ◽  
Mrna Levels ◽  
High Grade ◽  
Serous Ovarian Cancer ◽  
Expression Levels ◽  
Mrna Expression Levels

Abstract Background High-grade serous ovarian cancer (HGSOC) is the most common and lethal subtype of ovarian cancer. A growing body of evidence suggests tumor-supporting roles of several members of the kallikrein-related peptidase (KLK) family, including KLK5 and KLK7, in this cancer subtype. In normal physiology, KLK5 and KLK7 are the major proteases involved in skin desquamation. Moreover, in several cancer types KLK5 and KLK7 co-expression has been observed. Recently, we have shown that elevated KLK5 mRNA levels are associated with an unfavorable prognosis in HGSOC. Therefore, the aim of this study was to investigate the clinical significance of KLK7 mRNA expression and to explore its relation to KLK5 levels in HGSOC. Methods mRNA expression levels of KLK7 were quantified by qPCR in a well-characterized patient cohort afflicted with advanced high-grade serous ovarian cancer (FIGO III/IV, n = 139). Previously determined KLK5 mRNA as well as KLK5 and KLK7 antigen concentrations were used to evaluate the relationship between the expression patterns of both factors on the mRNA as well as protein level in tumor tissue of HGSOC patients. Results There were strong, significant positive correlations between KLK5 and KLK7 both at the mRNA and the protein level, suggesting coordinate expression of these proteases in HGSOC. In univariate analyses, elevated KLK7 levels as well as the combination of KLK5 + KLK7 (high and/or high versus low/low) were significantly associated with worse progression-free survival (PFS). High mRNA expression levels of KLK7 and the combination of KLK5 and KLK7 showed a trend towards significance for overall survival (OS). In multivariate analyses, KLK7 mRNA expression represented an unfavorable, statistically significant independent predictor for PFS and OS. Conclusions The findings imply that both increased KLK5 and KLK7 mRNA expression levels represent unfavorable prognostic biomarkers in advanced high-grade serous ovarian cancer, whereby multivariate analyses indicate that KLK7 mRNA exhibits a stronger predictive value as compared to KLK5 mRNA and the combination of KLK5 and KLK7.

BRCA1 mRNA Expression Levels Predict for Overall Survival in Ovarian Cancer after Chemotherapy

2007 ◽  
Vol 13 (24) ◽  
pp. 7413-7420 ◽  
Author(s):  
J. E. Quinn ◽  
C. R. James ◽  
G. E. Stewart ◽  
J. M. Mulligan ◽  
P. White ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Overall Survival ◽  
Mrna Expression ◽  
Expression Levels ◽  
Brca1 Mrna ◽  
Mrna Expression Levels

mRNA expression levels of the biological factors uPAR, uPAR-del4/5, and rab31, displaying prognostic value in breast cancer, are not clinically relevant in advanced ovarian cancer

2011 ◽  
Vol 392 (11) ◽  
Author(s):  
Matthias Kotzsch ◽  
Julia Dorn ◽  
Kristina Doetzer ◽  
Barbara Schmalfeldt ◽  
Janna Krol ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ovarian Cancer ◽  
Mrna Expression ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Tumor Tissue ◽  
Advanced Ovarian Cancer ◽  
Biological Factors ◽  
Expression Levels ◽  
Mrna Expression Levels

Abstract High tumor tissue mRNA expression of the tumor biological factors uPAR, uPAR-del4/5, or rab31 is associated with shorter distant metastasis-free and overall survival in breast cancer patients. To evaluate whether these factors are also clinically relevant in ovarian cancer, we quantified the respective mRNA levels in primary tumor tissue of advanced ovarian cancer patients (n=103) and evaluated their association with clinicopathological parameters and patients’ prognosis. mRNA expression levels of all three markers did not show any significant association with overall or progression-free survival, demonstrating that these factors have no prognostic value in advanced ovarian cancer.

scholarly journals Bioinformatics analysis of FOLR1 expression, functional enrichment, related signaling pathways and relationship with prognosis in ovarian cancer

Pteridines ◽  
2020 ◽  
Vol 31 (1) ◽  
pp. 46-54
Author(s):  
Yan Wang ◽  
Xiao Li ◽  
Pengpeng Qu
Keyword(s):  
Ovarian Cancer ◽  
Protein Expression ◽  
Mrna Expression ◽  
Cancer Patients ◽  
Progression Free Survival ◽  
Clustering Coefficient ◽  
Ppi Network ◽  
Free Survival ◽  
Expression Levels ◽  
Mrna Expression Levels

AbstractObjective To investigate folate-receptor 1 (FOLR1) expression in ovarian cancer and its association with patient prognosis.Methods TCGA and Oncomine databases were used to collect data about FOLR1 mRNA expression in multiple carcinomas. FOLR1 mRNA expression levels in ovarian cancer samples and corresponding adjacent normal ovary tissue were compared. A protein-protein interaction (PPI) network was constructed using the STRING database of FOLR1 and relevant genes. The overall survival (OS) and progression free survival (PFS) rates of ovarian cancer patients in high- and low- FOLR1 expression groups were compared by log-rank test. Sixty-six ovarian epithelial carcinoma samples were included in the study, and tumor specimens of the 66 cases were tested for FOLR1 protein expression by an immunohistochemistry assay.ResultsFOLR1 mRNA was significantly elevated in ovarian cancer compared to other carcinomas. FOLR1 mRNA expression levels were significantly higher in tumor tissues than in the corresponding normal tissues (P<0.05) of ovarian cancer patients. The PPI network indicated that the local clustering coefficient was 0.898, indicating that the PPI network was enriched significantly (P<0.05). The median PFS values were 22.39 and 19.00 months for lowand high-FOLR1 expression groups, respectively, with significant statistical difference between the two (HR=1.26, 95%CI:1.09-1.45, P<0.05). FOLR1 protein expression was correlated with tumor differentiation (P<0.05) in ovarian cancer patients. However, its levels were not correlated with patient age, tumor diameter, lymph node metastasis or FIGO stage (P>0.05).ConclusionFOLR1 is upregulated in epithelial ovarian cancer, and its expression is correlated with patients’ progression free survival, making it a valuable biomarker for prognosis.

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