Prognostic value of aberrant hypermethylation in pleural effusion of lung adenocarcinoma

Botana-Rial, Maribel; Chiara, Loretta De; Valverde, Diana; Leiro-Fernández, Virginia; Represas-Represas, Cristina; Campo-Pérez, Víctor del; Fernández-Villar, Alberto

doi:10.4161/cbt.22004

Cited by 13 publications

(8 citation statements)

References 27 publications

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“…However, promoter methylation of genes with biologic implication does not necessarily have similar prognostic impact. For example, in promoter methylation of certain TSGs in NSCLC, RAR-b and APC methylation have been reported to exhibit favorable outcomes in contrast with poor outcomes of RASSF1 methylation due to incomplete transcriptional silencing, compared with genetic alteration (48,49). In addition, individual promoter methylation is just a part of the epigenome-wide methylation status (50), and its suppressive role may be neutralized by differential methylation on CpG island shores, enhancers and repetitive elements in the noncoding areas of the genome, the activation of other signaling pathways, or the compensatory expression of functionally similar molecules such as the paralog group for HOXA9.…”

Section: Discussionmentioning

confidence: 99%

A Panel of Novel Detection and Prognostic Methylated DNA Markers in Primary Non–Small Cell Lung Cancer and Serum DNA

Ooki

Maleki

Tsay

et al. 2017

Clinical Cancer Research

131

109

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To establish a novel panel of cancer-specific methylated genes for cancer detection and prognostic stratification of early-stage non-small cell lung cancer (NSCLC). Identification of differentially methylated regions (DMR) was performed with bumphunter on "The Cancer Genome Atlas (TCGA)" dataset, and clinical utility was assessed using quantitative methylation-specific PCR assay in multiple sets of primary NSCLC and body fluids that included serum, pleural effusion, and ascites samples. A methylation panel of 6 genes (, and ) was selected from TCGA dataset. Promoter methylation of the gene panel was detected in 92.2% (83/90) of the training cohort with a specificity of 72.0% (18/25) and in 93.0% (40/43) of an independent cohort of stage IA primary NSCLC. In serum samples from the later 43 stage IA subjects and population-matched 42 control subjects, the gene panel yielded a sensitivity of 72.1% (31/41) and specificity of 71.4% (30/42). Similar diagnostic accuracy was observed in pleural effusion and ascites samples. A prognostic risk category based on the methylation status of, and refined the risk stratification for outcomes as an independent prognostic factor for an early-stage disease. Moreover, the paralog group for HOXA9, predominantly overexpressed in subjects with methylation, showed poor outcomes. Promoter methylation of a panel of 6 genes has potential for use as a biomarker for early cancer detection and to predict prognosis at the time of diagnosis. .

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Section: Discussionmentioning

confidence: 99%

A Panel of Novel Detection and Prognostic Methylated DNA Markers in Primary Non–Small Cell Lung Cancer and Serum DNA

Ooki

Maleki

Tsay

et al. 2017

Clinical Cancer Research

131

109

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“…And DNA methylation of CpG sites in the promoter regions or the first exon of genes is a frequent epigenetic event in cancers of the breast, liver, lung and others (Botana-Rial et al, 2012;Fujiwara et …”

Section: Introductionmentioning

confidence: 99%

Combined Effects Methylation of FHIT, RASSF1A and RARβ Genes on Non-Small Cell Lung Cancer in the Chinese Population

Li¹,

Deng²,

Tang³

2014

Asian Pacific Journal of Cancer Prevention

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Epigenetic modifications of tumour suppressor genes are involved in all kinds of human cancer. Aberrant promoter methylation is also considered to play an essential role in development of lung cancer, but the pathogenesis remains unclear.We collected the data of 112 subjects, including 56 diagnosed patients with lung cancer and 56 controls without cancer. Methylation of the FHIT, RASSF1A and RAR-β genes in DNA from all samples and the corresponding gene methylation status were assessed using the methylation-specific polymerase chain reaction (PCR, MSP). The results showed that the total frequency of separate gene methylation was significantly higher in lung cancer compared with controls (33.9-85.7 vs 0 %) (p<0.01).Similar outcomes were obtained from the aberrant methylation of combinations of any two or three genes (p<0.01). There was a tendency that the frequency of combinations of any two or three genes was higher in stageⅠ+Ⅱ than that in stage Ⅲ+Ⅳ with lung cancer. However, no significant difference was found across various clinical stages and clinic pathological gradings of lung cancer (p>0.05).These observations suggest that there is a significant association of promoter methylation of individual genes with lung cancer risk, and that aberrant methylation of combination of any two or three genes may be associated with clinical stage in lung cancer patients and involved in the initiation of lung cancer tumorigenesis. Methylation of FHIT, RASSF1A and RARβ genes may be related to progression of lung oncogenesis.

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“…However, the cut-off for interpreting cases as positive was not specified. 36 As in OC and breast carcinoma, no data are available, to the best of our knowledge, regarding malignant effusions from patients with uterine corpus or cervical carcinoma.…”

Section: Discussionmentioning

confidence: 99%

MGMT promoter methylation is a rare epigenetic change in malignant effusions

et al. 2019

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The serosal cavities are a frequent site of metastasis in cancer, with adenocarcinomas of the breast, lung, female genital system and gastrointestinal tract constituting the most common sites of origin. This anatomic site is additionally the primary localisation of malignant mesothelioma (MM). 1 Tumour cells in effusions possess cancer stem cell characteristics and are chemoresistant, rendering disease at this site refractory to therapy and fatal. 1,2 Better understanding of the molecular characteristics of cells in malignant effusions is therefore critical for improving treatment options for patients with advanced disease.Aberrant promoter methylation of tumour suppressor genes is commonly observed in cancer, and is mediated through the addition of a methyl group to the carbon-5 atom of cytosine in a cytosineguanine (CpG) dinucleotide. [3][4][5] O6-Methylguanine-DNA methyltransferase, encoded by the gene MGMT, located on 10q26, is a DNA repair enzyme that protects cells against the effect of alkylating agents by eliminating the alkylation of the O6 position of guanine in the DNA. 6,7 MGMT methylation has been reported in a wide spectrum of malignancies, including glioblastoma, 8 melanoma, 9 haematological cancers 10 and carcinomas, including those of ovarian, breast, gastrointestinal and lung origin. 11 The frequency of MGMT promoter methylation in ovarian carcinoma (OC) has ranged in different series from 0% to 39% using methylation-specific polymerase chain reaction assay, variation that probably owes much to the marked differences in the tumours studied with respect to histotype. 12-20 However, none of these studies

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Prognostic value of aberrant hypermethylation in pleural effusion of lung adenocarcinoma

Cited by 13 publications

References 27 publications

A Panel of Novel Detection and Prognostic Methylated DNA Markers in Primary Non–Small Cell Lung Cancer and Serum DNA

A Panel of Novel Detection and Prognostic Methylated DNA Markers in Primary Non–Small Cell Lung Cancer and Serum DNA

Combined Effects Methylation of FHIT, RASSF1A and RARβ Genes on Non-Small Cell Lung Cancer in the Chinese Population

MGMT promoter methylation is a rare epigenetic change in malignant effusions

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