Research Progress of DNA Methylation in Endometrial Cancer

Xu, Ting; Ding, Hongmei; Chen, Jie; Lei, Jiahui; Zhao, Meng; Ji, Bingyu; Chen, Youguo; Qin, Songbing; Gao, Qinqin

doi:10.3390/biom12070938

Cited by 13 publications

(10 citation statements)

References 122 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 29 Aberrant DNA methylation events have been reported for numerous tumor suppressor genes and oncogenes. 30 For instance, significant contributions of DNA methylation have been noted for genes such as PTEN , 31 RASSF1A 32 and BMP 33 in the context of endometrial carcinogenesis. Here, we uncovered that SIM2 methylation was inversely associated with its mRNA expression, despite that SIM2 promoter methylation level was higher in UCEC samples.…”

Section: Discussionmentioning

confidence: 99%

SIM2: Its Prognostic Significance and Oncogenic Role in Endometrial Carcinoma

Wei,

Zhao,

Tang

et al. 2024

OTT

View full text Add to dashboard Cite

Background Endometrial carcinoma ranks as the second most widespread malignancy affecting the reproductive system in females. Effective prognostic biomarkers are required to further improve survival rates for patients. Single-minded homolog 2 (SIM2) is known to participate in neurogenesis as a transcription factor. However, the potential role of SIM2 in endometrial carcinoma remains elusive. Methods Multiple public databases, including TIMER2.0, GEIPA2, UALCAN, LinkedOmics, BioGRID, DAVID and cBioPortal, were used to investigate SIM2 mRNA expression, SIM2-associated genes, PPI network, functional enrichment analysis, SIM2 gene alterations and methylation. The association between SIM2 expression and immune cell infiltrates was explored using GSVA. The effects of gene alterations and methylation on patient survival and CD8+T infiltration were examined using GSCA. Moreover, the prognostic potential of SIM2 was evaluated using COX regression, ROC curves and a nomogram model. Finally, the differential expression and function of SIM2 in UCEC were explored using qPCR, WB, CCK8 and Transwell assays. Results Our findings revealed the heightened expression of SIM2 in endometrial carcinoma, and that its DNA methylation and CNV alterations were correlated with immune infiltration and patients’ prognosis. Additionally, functional enrichment revealed the involvement of SIM2 in transcription regulation and signal transduction. Moreover, we performed cell-based experiments to corroborate the oncogenic function of SIM2 in facilitating cell proliferation, migration and invasion. Conclusion Collectively, these results suggest that SIM2 holds promise as both a potential prognostic indicator and a viable treatment target for endometrial carcinoma.

show abstract

Section: Discussionmentioning

confidence: 99%

SIM2: Its Prognostic Significance and Oncogenic Role in Endometrial Carcinoma

Wei,

Zhao,

Tang

et al. 2024

OTT

View full text Add to dashboard Cite

show abstract

“…Possible epigenetic mechanisms of endometrial cancer development and potential therapeutic targets have been recently reviewed [ 223 , 224 ]. The decreased promoter methylation frequency of VEGF, TNF, and HIF1α genes related to increased gene expression was noticed in endometrial cancer tissues as compared to a control study group [ 224 , 225 ]. Furthermore, genes frequently silenced by DNA promoter methylation in endometrial carcinoma were involved in DNA repair: MGMT and hMLH1 [ 226 ].…”

Section: Egcg Treatment In Malignant Gynecological Diseasesmentioning

confidence: 99%

Epigallocatechin Gallate for the Treatment of Benign and Malignant Gynecological Diseases—Focus on Epigenetic Mechanisms

Włodarczyk,

Ciebiera,

Nowicka

et al. 2024

Nutrients

View full text Add to dashboard Cite

The most common malignant gynecologic diseases are cervical, uterine, ovarian, vaginal, and vulvar cancer. Among them, ovarian cancer causes more deaths than any other cancer of the female reproductive system. A great number of women suffer from endometriosis, uterine fibroids (UFs), adenomyosis, dysmenorrhea, and polycystic ovary syndrome (PCOS), which are widespread benign health problems causing troublesome and painful symptoms and significantly impairing the quality of life of affected women, and they are some of the main causes of infertility. In addition to the available surgical and pharmacological options, the effects of supporting standard treatment with naturally occurring compounds, mainly polyphenols, are being studied. Catechins are responsible for the majority of potential health benefits attributed to green tea consumption. Epigallocatechin gallate (EGCG) is considered a non-toxic, natural compound with potential anticancer properties. Antioxidant action is its most common function, but attention is also drawn to its participation in cell division inhibition, apoptosis stimulation and epigenetic regulation. In this narrative review, we describe the role of EGCG consumption in preventing the development of benign reproductive disorders such as UF, endometriosis, and PCOS, as well as malignant gynecologic conditions. We discuss possible epigenetic mechanisms that may be related to the action of EGCG.

show abstract

“…30,39,40 This involves assessment of DNA hypermethylation at the CpG islands in the promoter region. 41,42 However, there have been rare reports of MLH1 promoter hypermethylation in those with MLH1-associated LS, where the methylation serves as a "second hit" in tumor development. 43 Constitutional methylation of MLH1 is also a rare but important mechanism of LS to recognize.…”

Section: Algorithms For Mmr/msi Assessment and Genetic Testing In Pat...mentioning

confidence: 99%

“…Given the high accuracy and low costs of IHC, this is usually the first step, followed by MLH1 methylation testing and then LS testing in cases lacking MLH1 promoter hypermethylation 30,39,40 . This involves assessment of DNA hypermethylation at the CpG islands in the promoter region 41,42 . However, there have been rare reports of MLH1 promoter hypermethylation in those with MLH1 ‐associated LS, where the methylation serves as a “second hit” in tumor development 43 .…”

Section: Algorithms For Mmr/msi Assessment and Genetic Testing In Pat...mentioning

confidence: 99%

A tale of two pathways: Review of immune checkpoint inhibitors in DNA mismatch repair‐deficient and microsatellite instability‐high endometrial cancers

Liu,

Weigelt

2024

Cancer

View full text Add to dashboard Cite

The DNA mismatch repair (MMR) pathway is critical for correcting DNA mismatches generated during DNA replication. MMR‐deficiency (MMR‐D) leads to microsatellite instability (MSI) associated with an increased mutation rate, driving cancer development. This is particularly relevant in endometrial cancer (EC) as 25%–30% of tumors are of MMR‐D/MSI‐high (MSI‐H) phenotype. Comprehensive assessment using immunohistochemistry (IHC) and sequencing‐based techniques are necessary to fully evaluate ECs given the importance of molecular subtyping in staging and prognosis. This also influences treatment selection as clinical trials have demonstrated survival benefits for immune checkpoint inhibitors (ICIs) alone and in combination with chemotherapy for MMR‐D/MSI‐H EC patients in various treatment settings. As a portion of MMR‐D/MSI‐H ECs are driven by Lynch syndrome, an inherited cancer predisposition syndrome that is also associated with colorectal cancer, this molecular subtype also prompts germline assessment that can affect at‐risk family members. Additionally, heterogeneity in the tumor immune microenvironment and tumor mutation burden (TMB) have been described by MMR mechanism, meaning MLH1 promoter hypermethylation versus germline/somatic MMR gene mutation, and this may affect response to ICI therapies. Variations by ancestry in prevalence and mechanism of MMR‐D/MSI‐H tumors have also been reported and may influence health disparities given observed differences in tumors of Black compared to White patients which may affect ICI eligibility. These observations highlight the need for additional prospective studies to evaluate the nuances regarding MMR‐D heterogeneity as well as markers of resistance to inform future trials of combination therapies to further improve outcomes for patients with EC.

show abstract

Research Progress of DNA Methylation in Endometrial Cancer

Cited by 13 publications

References 122 publications

SIM2: Its Prognostic Significance and Oncogenic Role in Endometrial Carcinoma

SIM2: Its Prognostic Significance and Oncogenic Role in Endometrial Carcinoma

Epigallocatechin Gallate for the Treatment of Benign and Malignant Gynecological Diseases—Focus on Epigenetic Mechanisms

A tale of two pathways: Review of immune checkpoint inhibitors in DNA mismatch repair‐deficient and microsatellite instability‐high endometrial cancers

Contact Info

Product

Resources

About