Integrative genome-wide expression and promoter DNA methylation profiling identifies a potential novel panel of ovarian cancer epigenetic biomarkers

Gloss, Brian; Patterson, Kate I.; Barton, Caroline; González, M.; Scurry, James; Hacker, Neville F.; Sutherland, Robert L.; O’Brien, Philippa M.; Clark, Susan J.

doi:10.1016/j.canlet.2011.12.003

Cited by 46 publications

(43 citation statements)

References 42 publications

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“…Such expression pattern has provided a potential for them to be used as cancer biomarkers at mRNA level. Another approach would be the evaluation of epigenetic changes in the promoter region of lncRNAs, which facilitates the discrimination of malignant tissues from normal counterparts as documented for a potential long-intergenic non-coding RNA gene (LOC134466) in SOC [60] . LncRNA expression profiling should be assessed in each cancer type as it has revealed that the most altered lncRNAs are different in distinct cancers [61] .…”

Section: Discussionmentioning

confidence: 99%

The Role of Long Non-Coding RNAs in Ovarian Cancer

Nikpayam

Tasharrofi

Sarrafzadeh

et al. 2017

IBJ

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Background: Ovarian cancer is the most fatal tumor of female's reproductive system, and several genetics and environmental factors are involved in its development. Various studies have already identified suitable biomarkers to facilitate the early detection, prognosis evaluation, and the assessment of treatment response. However, the aim of this review was to investigate the role of long non-coding RNAs (lncRNAs) in tumorigenesis process of ovarian cancer and their potential applications as ovarian cancer biomarkers. Methods: We performed an online literature search of the MEDLINE/PubMed databases using the key words ovarian cancer, lncRNA, and biomarker. Results: We found that several lncRNAs have been shown to be deregulated in ovarian cancer and the specific mechanism of their enrollment in ovarian cancer has been defined for a few of them. In addition, expression profiling has revealed an association between lncRNAs and patients' survival, metastasis potential as well as treatment response. Conclusions: Expression profiling as well as methylation analysis of lncRNAs in ovarian cancer may lead to the identification of novel biomarkers that can help in the classification of patients based on prognosis and treatment response.

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Section: Discussionmentioning

confidence: 99%

The Role of Long Non-Coding RNAs in Ovarian Cancer

Nikpayam

Tasharrofi

Sarrafzadeh

et al. 2017

IBJ

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“…The detection of methylated DNA as a biomarker of disease has several advantages over protein-based assays as defined regions of cancer-specific hypermethylated-DNA can be readily amplified from samples collected noninvasively using PCR-based technology (38). In addition, panels of DNA methylation probes specific to multiple genes can be readily assembled to further inform diagnosis, as shown for lung cancer (39), ovarian cancer (40), and prostate cancer (41). Although the detection of methylated BCL-2 has not been assessed in breast cancer patient serum, recent publications describe the detection of BCL-2 methylation in blood samples derived from patients with pancreatic cancer (42), and in urinary samples used to detect and monitor bladder cancer (43).…”

Section: Discussionmentioning

confidence: 99%

BCL-2 Hypermethylation Is a Potential Biomarker of Sensitivity to Antimitotic Chemotherapy in Endocrine-Resistant Breast Cancer

Stone

Cowley

Valdés-Mora

et al. 2013

Molecular Cancer Therapeutics

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Overexpression of the antiapoptotic factor BCL-2 is a frequent feature of malignant disease and is commonly associated with poor prognosis and resistance to conventional chemotherapy. In breast cancer, however, high BCL-2 expression is associated with favorable prognosis, estrogen receptor (ER) positivity, and low tumor grade, whereas low expression is included in several molecular signatures associated with resistance to endocrine therapy. In the present study, we correlate BCL-2 expression and DNA methylation profiles in human breast cancer and in multiple cell models of acquired endocrine resistance to determine whether BCL-2 hypermethylation could provide a useful biomarker of response to cytotoxic therapy. In human disease, diminished expression of BCL-2 was associated with hypermethylation of the second exon, in a region that overlapped a CpG island and an ER-binding site. Hypermethylation of this region, which occurred in 10% of primary tumors, provided a stronger predictor of patient survival (P ¼ 0.019) when compared with gene expression (n ¼ 522). In multiple cell models of acquired endocrine resistance, BCL-2 expression was significantly reduced in parallel with increased DNA methylation of the exon 2 region. The reduction of BCL-2 expression in endocrine-resistant cells lowered their apoptotic threshold to antimitotic agents: nocodazole, paclitaxel, and the PLK1 inhibitor BI2536. This phenomenon could be reversed with ectopic expression of BCL-2, and rescued with the BCL-2 inhibitor ABT-737. Collectively, these data imply that BCL-2 hypermethylation provides a robust biomarker of response to current and next-generation cytotoxic agents in endocrine-resistant breast cancer, which may prove beneficial in directing therapeutic strategy for patients with nonresectable, metastatic disease. Mol Cancer Ther; 12(9); 1874-85. Ó2013 AACR.

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“…Studies of promoter methylation patterns in tumor suppressor genes have yielded several promising methylated biomarker candidates. [2][3][4] In contrast to a gene or protein expression analysis, methylation can easily be detected using polymerase chain reaction (PCR)-based methods in both tumor material and body fluids. [5][6][7] TUSC3 (tumor suppressor candidate 3), originally named N33, was identified as a potential tumor suppressor gene in prostate cancer 8,9 and is located on chromosome band 8p22.…”

Section: Introductionmentioning

confidence: 99%

Methylation status of TUSC3 is a prognostic factor in ovarian cancer

Pils

Horak

Vaňhara

et al. 2012

Cancer

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BACKGROUND. Current prognostic information in ovarian cancer is based on tumor stage, tumor grade, and postoperative tumor size. Reliable molecular prognostic markers are scarce. In this article, the authors describe epigenetic events in a frequently deleted region on chromosome 8p22 that influence the expression of tumor suppressor candidate 3 (TUSC3), a putative tumor suppressor gene in ovarian cancer. METHODS. Messenger RNA expression and promoter hypermethylation of TUSC3 were studied in ovarian cancer cell lines and in tumor samples from 2 large, independent ovarian cancer cohorts using polymerase chain reaction-based methods. RESULTS. The results indicated that TUSC3 expression is decreased significantly because of promoter methylation in malignant ovarian tumors compared with benign controls. Almost 33% of ovarian cancer samples had detectable TUSC3 promoter methylation. Furthermore, methylation status of the TUSC3 promoter had a significant and independent influence on progression-free and overall survival. CONCLUSIONS. TUSC3 hypermethylation predicted progression-free and overall survival in ovarian cancer. The current observations suggested a role for N-glycosylating events in ovarian cancer pathogenesis in general and identified the epigenetic silencing of TUSC3 as a prognostic factor in this disease. Cancer 2013;119:946-54. V C 2012 American Cancer Society.KEYWORDS: TUSC3, methylation, ovarian cancer, glycosylation, progression-free survival, overall survival, biomarker.. INTRODUCTIONEpithelial ovarian cancer is the most lethal gynecologic malignancy and the fourth most frequent cause of cancer-related death among women in industrialized countries. 1 Because >75% of women are diagnosed with advanced disease (International Federation of Gynecology and Obstetrics [FIGO] stages III and IV), an early diagnosis presents 1 of the challenges of this disease. Patients with advanced ovarian cancer undergo intensive multimodal therapy consisting of cytoreductive surgery and (neo)adjuvant platinum-based and taxane-based chemotherapy. Regardless of the progress made in surgical and medical therapies over recent decades, the outcome for women with advanced ovarian cancer remains grim. Innovative, hypothesis-driven approaches to biomarker development remain essential even in the era of high-throughput sequencing and various omics. Studies of promoter methylation patterns in tumor suppressor genes have yielded several promising methylated biomarker candidates. [2][3][4] In contrast to a gene or protein expression analysis, methylation can easily be detected using polymerase chain reaction (PCR)-based methods in both tumor material and body fluids. [5][6][7] TUSC3 (tumor suppressor candidate 3), originally named N33, was identified as a potential tumor suppressor gene in prostate cancer 8,9 and is located on chromosome band 8p22. Known homozygous deletions of this region in pancreatic cell lines 10,11 and prostate cancer cell lines 12,13 contain no other cancer-related genes except TUSC3, although mutations of the T...

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Integrative genome-wide expression and promoter DNA methylation profiling identifies a potential novel panel of ovarian cancer epigenetic biomarkers

Cited by 46 publications

References 42 publications

The Role of Long Non-Coding RNAs in Ovarian Cancer

The Role of Long Non-Coding RNAs in Ovarian Cancer

BCL-2 Hypermethylation Is a Potential Biomarker of Sensitivity to Antimitotic Chemotherapy in Endocrine-Resistant Breast Cancer

Methylation status of TUSC3 is a prognostic factor in ovarian cancer

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