High-grade serous ovarian cancer primary tumor BRCA1 mRNA expression is a candidate biomarker for patient selection for intraperitoneal chemotherapy

2016 ◽  
Vol 141 ◽  
pp. 115
Author(s):  
B.L. Seagle ◽  
M. Dandapani ◽  
R. Samuelson ◽  
K. Eng ◽  
K.O. Odunsi ◽  
...  
2021 ◽  
Vol 11 ◽  
Author(s):  
Xiao-fei Li ◽  
Hai-yan Sun ◽  
Tian Hua ◽  
Hai-bo Zhang ◽  
Yun-jie Tian ◽  
...  

Aberrant DNA methylation is considered to play a critical role in the chemoresistance of epithelial ovarian cancer (EOC). In this study, we explored the relationship between hypermethylation of the Mahogunin Ring Finger 1 (MGRN1) gene promoter and primary chemoresistance and clinical outcomes in high-grade serous ovarian cancer (HGSOC) patients. The MALDI-TOF mass spectrometry assays revealed a strong association between hypermethylation of the MGRN1 upstream region and platinum resistance in HGSOC patients. Spearman’s correlation analysis revealed a significantly negative connection between the methylation level of MGRN1 and its expression in HGSOC. In vitro analysis demonstrated that knockdown of MGRN1 reduced the sensitivity of cells to cisplatin and that expression of EGR1 was significantly decreased in SKOV3 cells with low levels of MGRN1 expression. Similarly, EGR1 mRNA expression was lower in platinum-resistant HGSOC patients and was positively correlated with MGRN1 mRNA expression. Kaplan-Meier analyses showed that high methylation of the MGRN1 promoter region and low expression of MGRN1 were associated with worse survival of HGSOC patients. In multivariable models, low MGRN1 expression was an independent factor predicting poor outcome. Furthermore, low expression of EGR1 was also been confirmed to be significantly related to the poor prognosis of HGSOC patients by Kaplan-Meier. The hypermethylation of the MGRN1 promoter region and low expression of MGRN1 were associated with platinum resistance and poor outcomes in HGSOC patients, probably by altering EGR1 expression.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Weiwei Gong ◽  
Yueyang Liu ◽  
Eleftherios P. Diamandis ◽  
Marion Kiechle ◽  
Holger Bronger ◽  
...  

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.


2020 ◽  
pp. 1-4
Author(s):  
Irina Tsibulak ◽  
Verena Wieser ◽  
Hannah Welponer ◽  
Katharina Leitner ◽  
Hubert Hackl ◽  
...  

Author(s):  
Slavomir Krajnak ◽  
Jörg Jäkel ◽  
Katharina Anić ◽  
Roxana Schwab ◽  
Marcus Schmidt ◽  
...  

Abstract Purpose Integrins may be involved in the metastatic spread of high-grade serous ovarian cancer (HGSOC) which determines the therapeutical approach and prognosis. We investigated the integrin expression in primary tumor and metastases of advanced HGSOC. Methods The expression of integrin α2, α4, α5, α6, and β1 was assessed by immunostaining in tumor samples of the ovary, omentum, and peritoneum of each patient. Differences in integrin expression among tumor localizations and their association with clinicopathological parameters were examined by Fisher’s exact test. The impact of integrin expression on progression-free survival (PFS) and overall survival (OS) was examined by Cox regression and Kaplan–Meier analyses. Results Hundred and thirteen tumor samples of 40 HGSOC patients were examined. The expression of the integrins did not differ between the three tumor localizations (all p values > 0.05) with the exception of high expression of integrin α4 in primary tumor and omentum (52.5% versus 47.5%, p = 0.008) and primary tumor and peritoneum (52.5% versus 47.5%, p = 0.050). High expression of integrin α4 in peritoneum was associated with poorer PFS (HR 2.02 95% CI 1.01–4.05, p = 0.047), younger age (p = 0.047), and death (p = 0.046). Median PFS in patients with high expression of integrin α4 was 13.00 months, whereas median PFS in patients without high expression of integrin α4 was 21.00 months (p = 0.040). Expression of other integrins did not correlate with PFS or OS. Conclusion Expression of integrin α4 may be altered during the metastatic spread of HGSOC and affect prognosis, whereas expression of integrin α2, α5, α6, and β1 did not reveal any prognostic value.


2016 ◽  
Vol 141 ◽  
pp. 47-48
Author(s):  
A.A. Tone ◽  
J. Stewart ◽  
C. Virtanen ◽  
M.Q. Bernardini ◽  
S. Laframboise ◽  
...  

2018 ◽  
Vol 26 (6) ◽  
pp. 794-805 ◽  
Author(s):  
Nuri Yildirim ◽  
Gizem Calibasi Kocal ◽  
Zerrin Isik ◽  
Bahadır Saatli ◽  
Ugur Saygili ◽  
...  

Objectives: To investigate gene expression differences and related functions between primary tumor, malignant cells in ascites, and metastatic peritoneal implant in high-grade serous ovarian cancer. Methods: Biopsies from primary tumor, peritoneal implant, and ascites were collected from 10 patients operated primarily for high-grade, advanced-staged serous ovarian cancer. Total RNA isolation was performed from collected tissue biopsy and fluid samples, and RNA expression profile was measured. Messenger RNA expression profiles of 3 different groups were compared. Functional analyses of candidate genes were carried out by gene ontology and pathway analysis. Results: There were significant differences in the expression of 5 genes between primary tumor and peritoneal implant, 979 genes between primary tumor and malignant cells in ascites, and 649 genes between peritoneal implant and malignant cells in ascites. Three commonly enriched gene ontology functions between “primary tumor and malignant cells in the ascites” and “peritoneal implant and malignant cells in the ascites” were protein deubiquitination, ubiquitin-dependent protein catabolism, and apoptotic processes. All genes related to these functions belonged to USP17 gene family. Conclusion: Gene expression difference between primary tumor and the peritoneal implant is not as much as the difference between primary tumor and free cells in the ascites. These results show that malignant cells in the ascites return into its genetic origin after they invade on the peritoneum. Significantly increased expression of DUB-enzyme genes, SNAR gene family, and ribosomal pathway genes in epithelial–mesenchymal transition suggests that this regulation is ubiquitin–proteasome dependent. Especially, this is the first study that offers USP17 as a potential target for epithelial–mesenchymal transition.


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