Epigenetic changes as prognostic predictors in endometrial carcinomas

Farkas, Sanja A.; Sorbe, Bengt; Nilsson, Torbjörn

doi:10.1080/15592294.2016.1252891

Cited by 21 publications

(17 citation statements)

References 30 publications

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“…Overall, few studies have evaluated the potential predictive role of DNA methylation patterns in EC prognosis. Although TBX2, CHST11, and NID2 were identified as having specific DNA methylation signatures for unfavorable clinical predictive and prognostic factors and a prognostic model that contained 15 methylation markers was recently established to distinguish EC patients with a poorer prognosis 18,19 biomarkers with higher accuracy should be investigated to assist in prognosis prediction for EC patients.…”

Section: Discussionmentioning

confidence: 99%

“…During recent decades, a few specific DNA methylation signatures associated with high-risk EC and a series of altered methylation genes associated with unfavorable prognostic factors have been identified, such as TBX2, CHST11, PTEN and NID2 18–20 . Even though advanced studies permit genome-wide screening at the DNA methylation or mRNA expression level, the mechanisms of DNA methylation that are involved in the regulation of gene expression and affect prognosis in EC remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Identification of prognosis markers for endometrial cancer by integrated analysis of DNA methylation and RNA-Seq data

Huo

Sun

Cao

et al. 2019

Sci Rep

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Endometrial cancer is highly malignant and has a poor prognosis in the advanced stage, thus, prediction of its prognosis is important. DNA methylation has rapidly gained clinical attention as a biomarker for diagnostic, prognostic and predictive purposes in various cancers. In present study, differentially methylated positions and differentially expressed genes were identified according to DNA methylation and RNA-Seq data. Functional analyses and interaction network were performed to identify hub genes, and overall survival analysis of hub genes were validated. The top genes were evaluated by immunohistochemical staining of endometrial cancer tissues. The gene function was evaluated by cell growth curve after knockdown CDC20 and CCNA2 of endometrial cancer cell line. A total of 329 hypomethylated highly expressed genes and 359 hypermethylated lowly expressed genes were identified, and four hub genes were obtained according to the interaction network. Patients with low expression of CDC20 and CCNA2 showed better overall survival. The results also were demonstrated by the immunohistochemical staining. Cell growth curve also demonstrated that knockdown CDC20 and CCNA2 can suppress the cell proliferation. We have identified two aberrantly methylated genes, CDC20 and CCNA2 as novel biomarkers for precision diagnosis in EC.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Identification of prognosis markers for endometrial cancer by integrated analysis of DNA methylation and RNA-Seq data

Huo

Sun

Cao

et al. 2019

Sci Rep

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“…However, combination of any two genes increased sensitivity to 91.8% with 95.5% specificity [30]. Another study identified an association between poor prognostic factors in high-risk (grade three) tumours and genes TBX2, CHST11 and NID2 [31].…”

Section: Dna Methylationmentioning

confidence: 99%

The role of biomarkers in endometrial cancer and hyperplasia: a literature review

et al. 2019

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Introduction: Endometrial cancer is the most common gynaecological cancer and its incidence is rising due to increasing obesity rates. We are also seeing an increasing trend of young women diagnosed with either endometrial cancer or its precancerous state, endometrial hyperplasia. Diagnosis is dependent on invasive testing and there is no screening tool available for either general or high-risk population groups.Whilst vast amounts of research have been undertaken in higher-profile cancers such as ovarian and cervical, endometrial cancer is comparatively less investigated. Aim: In this literature review, we summarise the existing literature in understanding the role of tumour biomarkers for endometrial cancer and its preceding condition of endometrial hyperplasia. Method: NICE Healthcare Databases Search tool was used to search Embase, Medline and PubMed databases for relevant articles. Conclusion: There is currently no routinely used biomarker in endometrial cancer for diagnostic or prognostic purposes. Given the establishment of new genomic classifications of endometrial cancers, the use of biomarkers to drive therapeutic approaches will be the cornerstone for individualised cancer care in the coming decades. ARTICLE HISTORY

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“…On the other hand, TBX2 inhibits cell cycle progression in lung adenocarcinoma (15) and its expression is decreased in lung cancers compared to normal tissue (16). Furthermore, TBX2 methylation has been associated with a poor prognosis in chronic lymphocytic leukemia (17), endometrial cancer (18) and bladder cancer (19). Thus, TBX2 may also exert an anti-tumor activity depending on the context and cellular origin of cancers.…”

Section: Dna Demethylation Agent 5azadc Downregulates Hpv16 E6 Expresmentioning

confidence: 99%

DNA demethylation agent 5azadC downregulates HPV16 E6 expression in cervical cancer cell lines independently of TBX2 expression

Perrard¹,

Morel

Meznad³

et al. 2019

Oncol Lett

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HPV16 is the most carcinogenic human papillomavirus and causes >50% of cervical cancers, the majority of anal cancers and 30% of oropharyngeal squamous cell carcinomas. HPV carcinogenesis relies on the continuous expression of the two main viral oncoproteins E6 and E7 that target >150 cellular proteins. Among them, epigenetic modifiers, including DNA Methyl Transferases (DNMT), are dysregulated, promoting an aberrant methylation pattern in HPV-positive cancer cells. It has been previously reported that the treatment of HPV-positive cervical cancer cells with DNMT inhibitor 5-aza-2'-deoxycytidine (5azadC) caused the downregulation of E6 expression due to mRNA destabilization that was mediated by miR-375. Recently, the T-box transcription factor 2 (TBX2) has been demonstrated to repress HPV LCR activity. In the current study, the role of TBX2 in E6 repression was investigated in HPV16 cervical cancer cell lines following 5azadC treatment. A decrease of E6 expression was accompanied by p53 and p21 restoration. While TBX2 mRNA was upregulated in 5azadC-treated SiHa and Ca Ski cells, TBX2 protein was not detectable. Furthermore, the overexpression of TBX2 protein in cervical cancer cells did not allow the repression of E6 expression. The TBX2 transcription factor is therefore unlikely to be associated with the repression of E6 following 5azadC treatment of SiHa and Ca Ski cells.

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Epigenetic changes as prognostic predictors in endometrial carcinomas

Cited by 21 publications

References 30 publications

Identification of prognosis markers for endometrial cancer by integrated analysis of DNA methylation and RNA-Seq data

Identification of prognosis markers for endometrial cancer by integrated analysis of DNA methylation and RNA-Seq data

The role of biomarkers in endometrial cancer and hyperplasia: a literature review

DNA demethylation agent 5azadC downregulates HPV16 E6 expression in cervical cancer cell lines independently of TBX2 expression

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