Loss of Expression of Cyclin D2 by Aberrant DNA Methylation: a Potential Biomarker in Vietnamese Breast Cancer Patients

Truong, Phuong Kim; Lao, Thuan Duc; Doan, Thao Phuong Thi; Le, Thuy Ai Huyen

doi:10.7314/apjcp.2015.16.6.2209

Cited by 12 publications

(8 citation statements)

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“…Some studies demonstrated that absence of CCND2 expression is associated with promoter hypermethylation in GC, 57 as well as in breast, lung, prostate, and liver cancers. 58 – 62 But some studies showed that CCND2 mRNA is overexpressed in GC. 36 , 63 – 65 Therefore, more studies are needed to evaluate the expression of CCND2 in GC to resolve the conflicting picture.…”

Section: Discussionmentioning

confidence: 99%

Clinical significance and biological roles of cyclins in gastric cancer

Zhang¹,

Li²,

Wang³

et al. 2018

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Background and aimCyclins have been reported to be overexpressed with poor prognosis in several human cancers. However, limited numbers of studies evaluated the expressions and prognostic roles of cyclins in gastric cancer (GC). We aim to evaluate the expressions and prognostic roles of cyclins. Also, further efforts were made to explore biological function of the differentially expressed cyclins.MethodsCyclins expressions were analyzed by Oncomine and The Cancer Genome Atlas datasets, and the prognostic roles of cyclins in GC patients were investigated by the Kaplan–Meier Plotter database. Then, a comprehensive PubMed literature search was performed to identify expression and prognosis of cyclins in GC. Biological functions of the differentially expressed cyclins were explored through Enrich R platform, and KEGG and transcription factor were analyzed.ResultsThe expression levels of CCNA2 (cyclin A2), CCNB1 (cyclin B1), CCNB2 (cyclin B2), and CCNE1 (cyclin E1) mRNAs were identified to be significantly higher in GC tissues than in normal tissues in both Oncomine and The Cancer Genome Atlas datasets. High expressions of CCNA2, CCNB1, and CCNB2 mRNAs were identified to be related with poor overall survival in Kaplan–Meier Plotter dataset. Evidence from clinical studies showed that CCNB1 was related with overall survival in GC patients. Cyclins were associated with several biological pathways, including cell cycle, p53 signaling pathway, FoxO signaling pathway, viral carcinogenesis, and AMPK signaling pathway. Enrichment analysis also showed that cyclins interacted with some certain transcription factors, such as FOXM1, SIN3A, NFYA, and E2F4.ConclusionBased on our results, high expressions of cyclins were related with poor prognosis in GC patients. The above information might be useful for better understanding the clinical and biological roles of cyclins mRNA and guiding individualized treatments for GC patients.

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Section: Discussionmentioning

confidence: 99%

Clinical significance and biological roles of cyclins in gastric cancer

Zhang¹,

Li²,

Wang³

et al. 2018

OTT

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“…Even though the relationship between HPV and aberrant methylation in CC is not well understood, some reports suggested E6 and E7 oncoprotein of high-risk HPV increase the expression and activity of DNMT1, which is the major mammalian enzyme responsible for maintaining CpG methylation patterns in the cell following replication, through the suppression of TSG p53 [25,26]. In addition, HPV-16 E7 bind to DNMT1 and precipitate, upregulate DNA methyltransferase activity, increased the hypermethylation in many TSGs led to the development of human cancer of cervix [22]. In this study, the hypermethylation of DAPK promoter was detectable in liquid-based Pap test sample by MSP method.…”

Section: Discussionmentioning

confidence: 99%

“…Given examples, in our previous studies, the significant association between the hypermethylation of many TSGs, including p16INK4α, BRCA1, Cyclin D2, GSTP1, and RASSF1A, and breast cancer were reported. However, notably, there is no data regarding DAPK promoter hypermethylation in Vietnamese, which is considered involving CC [20][21][22]. Therefore, the aim at this study is to evaluate the frequency of hypermethylation of CpG which is belonged to promoter of DAPK gene, in Vietnamese population, as well as, to study about the association between the epigenetic event, hypermethylation, and high-risk HPV infection leading to the cancer of cervix.…”

Section: Introductionmentioning

confidence: 99%

Identification of Frequent Promoter Methylation of Death-Associated Protein Kinase in Liquid-Based Papanicolaous Test Samples in Vietnamese Population

Truong

Lao

2017

Asian J Pharm Clin Res

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Objective: The infection of high-risk human papillomavirus (HPV) genotypes, particularly HPV-16 and HPV-18, is known to cause cervical cancer (CC); however, aberrant DNA methylation of death-associated protein kinase (DAPK), a member of tumor suppressor gene family, are required for cervical tumorigenesis. The aim of our study was to evaluate the hypermethylation frequency of CpG belonged to DAPK promoter, in Vietnamese patients, as well as to study about the association between hypermethylation, and high-risk HPV infection leading to CC.Methods: Methylation-specific-polymerase chain reaction (MSP) was performed to analyze methylation status from 109 liquid-based papanicolaous test samples, collected from local hospital and were identified whether HPV/or non-HPV, high-risk/low-risk HPV infection, then was confirmed by sequencing. Results:In the case of high-risk HPV infection, the frequency of DAPK gene hypermethylation was 66.67% (24 of 36 cases). Meanwhile, low hypermethylation status was found in low-risk and non-HPV infection, counting for 12.0% (3 of 25 cases), 2.1% (1 of 48 cases), respectively. Significant association of DAPK hypermethylation with high-risk, low-risk, and non-HPV infection was observed (p<0.0001). The DAPK hypermethylation increased the possibility to CC in the case of high-risk HPV infected with high incidence: Odds ratio=34.5 (95% confidence interval [CI]=10.15-117.23, p<0.01), relative risk=12.2 (95% CI=4.56-32.42, p<0.01). Conclusion:Based on those data, it suggested that MSP carried out on noninvasive samples will lead to potential method to screening, diagnosis and early diagnosis of cervical carcinoma in Vietnamese population.

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“…Of these genes Cyclin D2 exhibited a stark contrast in frequency between AAs (64%) and Caucasians (19%). While some of these genes may not be linked to prognosis, hypermethylation of Cyclin D2 and RASSF1A are both associated with higher relapse rates and poor overall survival (91)(92)(93).…”

Section: Insights From Other Cancersmentioning

confidence: 99%

Lung cancer early detection and health disparities: the intersection of epigenetics and ethnicity

Lerner¹,

Winn²,

Hulbert³

2018

J. Thorac. Dis.

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Lung cancer is the most prominent cause of cancer-related mortality. Significant disparities in incidence and outcome characterize the disease's manifestations among ethnically and racially diverse populations. Complete surgical resection is the most effective curative treatment. However, success relies on early tumor detection. The National Lung Cancer Screening trial showed that lung cancer related mortality can be reduced by the use of low-dose CT (LDCT) screening. However, this test is plagued by a high false positive rate of 97% and the device itself is limited to designated cancer centers due to its expense and size. This restriction makes it difficult for underserved groups to access LDCT screening, the current standard of care. Highly sensitive and specific epigenetic DNA methylation-based biomarkers have the potential to work independently or in conjunction with LDCT screening to identify early-stage tumors. These tests could reduce unnecessary invasive confirmatory diagnostic tests and their associated morbidity and mortality.These tests also have the opportunity to bring lung cancer screening to the community thereby reducing unequal accessibility. However, epigenetic alterations are closely linked to the interplay between hereditary and environmental factors such as diet, lifestyle, ethnic ancestry, toxin exposure, residential segregation, and disparate community support structures. Despite this, the overwhelming number of early detection DNA methylation biomarker studies to date have either failed to control for ethnicity or have employed heavily Caucasian-biased patient cohorts. This review seeks to summarize the literature related to the early detection of lung cancer through molecular biomarkers among different ethnicities. Ethnical specific epigenetic biomarkers have the potential to be the first step towards an accessible, available personalized medicine approach to cancer through liquid biopsy.

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Loss of Expression of Cyclin D2 by Aberrant DNA Methylation: a Potential Biomarker in Vietnamese Breast Cancer Patients

Cited by 12 publications

References 10 publications

Clinical significance and biological roles of cyclins in gastric cancer

Clinical significance and biological roles of cyclins in gastric cancer

Identification of Frequent Promoter Methylation of Death-Associated Protein Kinase in Liquid-Based Papanicolaous Test Samples in Vietnamese Population

Lung cancer early detection and health disparities: the intersection of epigenetics and ethnicity

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