scholarly journals HOXA11 DNA methylation-A novel prognostic biomarker in ovarian cancer

2008 ◽  
Vol 123 (3) ◽  
pp. 725-729 ◽  
Author(s):  
Heidi Fiegl ◽  
Gudrun Windbichler ◽  
Elisabeth Mueller-Holzner ◽  
Georg Goebel ◽  
Matthias Lechner ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Prognostic Biomarker

scholarly journals Hypermethylation of mismatch repair gene hMSH2 associates with platinum-resistant disease in epithelial ovarian cancer

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Hua Tian ◽  
Li Yan ◽  
Li Xiao-fei ◽  
Sun Hai-yan ◽  
Chen Juan ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Ovarian Cancer ◽  
Dna Methylation ◽  
Epithelial Ovarian Cancer ◽  
Upstream Region ◽  
Platinum Resistance ◽  
Maldi Tof Mass Spectrometry ◽  
Platinum Resistant ◽  
Aberrant Dna Methylation ◽  
Low Expression

Abstract Purpose One major reason of the high mortality of epithelial ovarian cancer (EOC) is due to platinum-based chemotherapy resistance. Aberrant DNA methylation may be a potential mechanism underlying the development of platinum resistance in EOC. The purpose of this study is to discover potential aberrant DNA methylation that contributes to drug resistance. Methods By initially screening of 16 platinum-sensitive/resistant samples from EOC patients with reduced representation bisulfite sequencing (RRBS), the upstream region of the hMSH2 gene was discovered hypermethylated in the platinum-resistant group. The effect of hMSH2 methylation on the cellular response to cisplatin was explored by demethylation and knockdown assays in ovarian cancer cell line A2780. Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry was employed to examine the methylation levels of hMSH2 upstream region in additional 40 EOC patient samples. RT-qPCR and IHC assay was used to detect the hMSH2 mRNA and protein expression in extended 150 patients. Results RRBS assay discovered an upstream region from − 1193 to − 1125 of hMSH2 was significant hypermethylated in resistant EOC patients (P = 1.06 × 10−14). In vitro analysis demonstrated that global demethylation increased cisplatin sensitivity along with a higher expression of the hMSH2 mRNA and protein. Knockdown hMSH2 reduced the cell sensitivity to cisplatin. MALDI-TOF mass spectrometry assay validated the strong association of hypermethylation of hMSH2 upstream region with platinum resistance. Spearman’s correlation analysis revealed a significantly negative connection between methylation level of hMSH2 upstream region and its expression. The Kaplan-Meier analyses showed the high methylation of hMSH2 promoter region, and its low expressions are associated with worse survival. In multivariable models, hMSH2 low expression was an independent factor predicting poor outcome (P = 0.03, HR = 1.91, 95%CI = 1.85–2.31). Conclusion The hypermethylation of hMSH2 upstream region is associated with platinum resistant in EOC, and low expression of hMSH2 may be an index for the poor prognosis.

scholarly journals The levels of soluble cMET ectodomain in the blood of patients with ovarian cancer are an independent prognostic biomarker

2021 ◽  
Author(s):  
Daniel Martin Klotz ◽  
Theresa Link ◽  
Maren Goeckenjan ◽  
Pauline Wimberger ◽  
Jan Dominik Kuhlmann
Keyword(s):  
Ovarian Cancer ◽  
Prognostic Biomarker

Sab concentrations indicate chemotherapeutic susceptibility in ovarian cancer cell lines

2018 ◽  
Vol 475 (21) ◽  
pp. 3471-3492 ◽  
Author(s):  
Iru Paudel ◽  
Sean M. Hernandez ◽  
Gilda M. Portalatin ◽  
Tara P. Chambers ◽  
Jeremy W. Chambers
Keyword(s):  
Ovarian Cancer ◽  
Cell Lines ◽  
Ovarian Cancer Cell ◽  
Prognostic Biomarker ◽  
Chemotherapeutic Agents ◽  
Mitochondrial Outer Membrane ◽  
Expression Data ◽  
Apoptotic Pathway ◽  
Gynecological Malignancy ◽  
Ovarian Cancer Cell Lines

The occurrence of chemotherapy-resistant tumors makes ovarian cancer (OC) the most lethal gynecological malignancy. While many factors may contribute to chemoresistance, the mechanisms responsible for regulating tumor vulnerability are under investigation. Our analysis of gene expression data revealed that Sab, a mitochondrial outer membrane (MOM) scaffold protein, was down-regulated in OC patients. Sab-mediated signaling induces cell death, suggesting that this apoptotic pathway is diminished in OC. We examined Sab expression in a panel of OC cell lines and found that the magnitude of Sab expression correlated to chemo-responsiveness; wherein, OC cells with low Sab levels were chemoresistant. The Sab levels were reflected by a corresponding amount of stress-induced c-Jun N-terminal kinase (JNK) on the MOM. BH3 profiling and examination of Bcl-2 and BH3-only protein concentrations revealed that cells with high Sab concentrations were primed for apoptosis, as determined by the decrease in pro-survival Bcl-2 proteins and an increase in pro-apoptotic BH3-only proteins on mitochondria. Furthermore, overexpression of Sab in chemoresistant cells enhanced apoptotic priming and restored cellular vulnerability to a combination treatment of cisplatin and paclitaxel. Contrariwise, inhibiting Sab-mediated signaling or silencing Sab expression in a chemosensitive cell line resulted in decreased apoptotic priming and increased resistance. The effects of silencing on Sab on the resistance to chemotherapeutic agents were emulated by the silencing or inhibition of JNK, which could be attributed to changes in Bcl-2 protein concentrations induced by sub-chronic JNK inhibition. We propose that Sab may be a prognostic biomarker to discern personalized treatments for OC patients.

scholarly journals Development and Validation of a Prognostic Nomogram Based on DNA Methylation-Driven Genes for Patients With Ovarian Cancer

2021 ◽  
Vol 12 ◽  
Author(s):  
Min Zhou ◽  
Shasha Hong ◽  
Bingshu Li ◽  
Cheng Liu ◽  
Ming Hu ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Mrna Expression ◽  
Risk Score ◽  
Cox Regression ◽  
Expression Profiles ◽  
Figo Stage ◽  
Prognostic Indicator ◽  
Tissue Expression ◽  
The Cancer Genome Atlas

Background: DNA methylation affects the development, progression, and prognosis of various cancers. This study aimed to identify DNA methylated-differentially expressed genes (DEGs) and develop a methylation-driven gene model to evaluate the prognosis of ovarian cancer (OC).Methods: DNA methylation and mRNA expression profiles of OC patients were downloaded from The Cancer Genome Atlas, Genotype-Tissue Expression, and Gene Expression Omnibus databases. We used the R package MethylMix to identify DNA methylation-regulated DEGs and built a prognostic signature using LASSO Cox regression. A quantitative nomogram was then drawn based on the risk score and clinicopathological features.Results: We identified 56 methylation-related DEGs and constructed a prognostic risk signature with four genes according to the LASSO Cox regression algorithm. A higher risk score not only predicted poor prognosis, but also was an independent poor prognostic indicator, which was validated by receiver operating characteristic (ROC) curves and the validation cohort. A nomogram consisting of the risk score, age, FIGO stage, and tumor status was generated to predict 3- and 5-year overall survival (OS) in the training cohort. The joint survival analysis of DNA methylation and mRNA expression demonstrated that the two genes may serve as independent prognostic biomarkers for OS in OC.Conclusion: The established qualitative risk score model was found to be robust for evaluating individualized prognosis of OC and in guiding therapy.

scholarly journals Telomere length is a prognostic biomarker in elderly advanced ovarian cancer patients: a multicenter GINECO study

Aging ◽  
2015 ◽  
Vol 7 (12) ◽  
pp. 1066-1074 ◽  
Author(s):  
Claire Falandry ◽  
Béatrice Horard ◽  
Amandine Bruyas ◽  
Eric Legouffe ◽  
Jacques Cretin ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Telomere Length ◽  
Cancer Patients ◽  
Prognostic Biomarker ◽  
Advanced Ovarian Cancer

scholarly journals Genome-wide DNA methylome analysis identifies methylation signatures associated with survival and drug resistance of ovarian cancers

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
David W. Chan ◽  
Wai-Yip Lam ◽  
Fushun Chen ◽  
Mingo M. H. Yung ◽  
Yau-Sang Chan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Dna Methylation ◽  
Drug Resistance ◽  
Poor Prognosis ◽  
Ovarian Cancer Cells ◽  
High Grade ◽  
Dna Hypermethylation ◽  
Demethylating Agents ◽  
Ovarian Cancers ◽  
The Impact

Abstract Background In contrast to stable genetic events, epigenetic changes are highly plastic and play crucial roles in tumor evolution and development. Epithelial ovarian cancer (EOC) is a highly heterogeneous disease that is generally associated with poor prognosis and treatment failure. Profiling epigenome-wide DNA methylation status is therefore essential to better characterize the impact of epigenetic alterations on the heterogeneity of EOC. Methods An epigenome-wide association study was conducted to evaluate global DNA methylation in a retrospective cohort of 80 mixed subtypes of primary ovarian cancers and 30 patients with high-grade serous ovarian carcinoma (HGSOC). Three demethylating agents, azacytidine, decitabine, and thioguanine, were tested their anti-cancer and anti-chemoresistant effects on HGSOC cells. Results Global DNA hypermethylation was significantly associated with high-grade tumors, platinum resistance, and poor prognosis. We determined that 9313 differentially methylated probes (DMPs) were enriched in their relative gene regions of 4938 genes involved in small GTPases and were significantly correlated with the PI3K-AKT, MAPK, RAS, and WNT oncogenic pathways. On the other hand, global DNA hypermethylation was preferentially associated with recurrent HGSOC. A total of 2969 DMPs corresponding to 1471 genes were involved in olfactory transduction, and calcium and cAMP signaling. Co-treatment with demethylating agents showed significant growth retardation in ovarian cancer cells through differential inductions, such as cell apoptosis by azacytidine or G2/M cell cycle arrest by decitabine and thioguanine. Notably, azacytidine and decitabine, though not thioguanine, synergistically enhanced cisplatin-mediated cytotoxicity in HGSOC cells. Conclusions This study demonstrates the significant association of global hypermethylation with poor prognosis and drug resistance in high-grade EOC and highlights the potential of demethylating agents in cancer treatment. Graphic abstract

scholarly journals A Liquid-Liquid Phase Separation-Related Gene Signature as Prognostic Biomarker for Epithelial Ovarian Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Yan Qiu ◽  
Min Pan ◽  
Xuemei Chen
Keyword(s):  
Ovarian Cancer ◽  
Phase Separation ◽  
Prognostic Biomarker ◽  
Risk Group ◽  
Risk Index ◽  
Gene Signature ◽  
Related Gene ◽  
Data Set ◽  
Test Set ◽  
Liquid Liquid Phase Separation

ObjectiveThe aim of the present study was to construct and test a liquid-liquid phase separation (LLPS)-related gene signature as a prognostic tool for epithelial ovarian cancer (EOC).Materials and MethodsThe data set GSE26712 was used to screen the differentially expressed LLPS-related genes. Functional enrichment analysis was performed to reveal the potential biological functions. GSE17260 and GSE32062 were combined as the discovery to construct an LLPS-related gene signature through a three-step analysis (univariate Cox, least absolute shrinkage and selection operator, and multivariate Cox analyses). The EOC data set from The Cancer Genome Atlas as the test set was used to test the LLPS-related gene signature.ResultsThe differentially expressed LLPS-related genes involved in several cancer-related pathways, such as MAPK signaling pathway, cell cycle, and DNA replication. Eleven genes were selected to construct the LLPS-related gene signature risk index as prognostic biomarker for EOC. The risk index could successfully divide patients with EOC into high- and low-risk groups. The patients in high-risk group had significantly shorter overall survival than those with in low-risk group. The LLPS-related gene signature was validated in the test set and may be an independent prognostic factor compared to routine clinical features.ConclusionWe constructed and validated an LLPS-related gene signature as a prognosis tool in EOC through integrated analysis of multiple data sets.

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