Methylation of multiple genes as a candidate biomarker in non-small cell lung cancer

Zhang, Youwei; Wang, Rui; Song, Haiyan; Huang, Guichun; Yi, Jun; Zheng, Yun; Wang, Jinghua; Chen, Longbang

doi:10.1016/j.canlet.2010.12.011

Cited by 188 publications

(130 citation statements)

References 40 publications

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“…(22)(23)(24) A subset of the CpG island methylator phenotype (CIMP), originally established in colorectal carcinoma, (25,26) is characterized by the synchronous hypermethylation of multiple promoter CpG island regions and peculiar clinicopathological findings. Although several reports have indicated that CIMP is also distinguishable in NSCLC and is associated with a poor prognosis, (27,28) we have failed to distinguish the phenotype in the previous study regarding the methylation of the promoter regions of numerous protein-coding genes. (29) In the present study, we analyzed whether the concordant hypermethylation of multiple miRNA loci results in characteristics similar to those of CIMP.…”

Section: Discussioncontrasting

confidence: 65%

CpG island methylation of microRNAs is associated with tumor size and recurrence of non‐small‐cell lung cancer

Kitano

Watanabe²,

Emoto³

et al. 2011

Cancer Science

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We investigated whether the CpG island methylation of certain microRNAs was associated with the clinicopathological features and the prognosis of non-small-cell lung cancer. The methylation of mir-152, -9-3, -124-1, -124-2, and -124-3 was analyzed in 96 nonsmall-cell lung cancer specimens using a combined bisulfite restriction analysis. The median observation period was 49.5 months. The methylation of mir-9-3, -124-2, and -124-3 was individually associated with an advanced T factor independent of age, sex, and smoking habit. Moreover, the methylation of multiple microRNA loci was associated with a poorer progression-free survival in a univariate analysis. Our result enlightens the accumulation of aberrant DNA methylation which occurs in concordance with the tumor progression. (Cancer Sci 2011; 102: 2126-2131 L ung cancer is the leading cause of cancer-related mortality in the world,(1) and non-small-cell lung cancer (NSCLC) is the most common type. Surgical resection remains the only curative treatment for NSCLC. Identifying factors that are associated with aggressive disease may lead to the development of novel biomarkers and the identification of therapeutic targets that can help reduce the burden of this disease.MicroRNAs (miRNAs) are a class of small non-coding RNAs that negatively regulate target gene expression by accelerating the degradation of mRNA and translational inhibition, with potentially hundreds of target mRNAs.(2) They influence a variety of cellular functions including proliferation, differentiation, and apoptosis.(3) Specific miRNAs can behave as either tumor suppressor genes or oncogenes, depending on the tissue type and the presence of specific targets. (4,5) More than 100 species of known miRNAs are embedded within or near the CpG islands of the human genome and are potentially subject to control by epigenetic alterations such as DNA methylation and histone modification. Systematic assessments of miRNA expression and epigenetic modifications among cell lines and primary tumor specimens have revealed the existence of the epigenetic regulation of miRNAs in multiple tumor types. (6)(7)(8)(9) The goals of this study were to explore possible relationships between the methylation profiles of miRNAs and the clinicopathological characteristics of NSCLC patients and to identify new specific methylation markers capable of detecting advanced pathological features.In the present study, the methylation status of five miRNA loci within five separate CpG islands was determined in 96 NSCLC tissue specimens. The choice of the miRNAs was based on our previous study (9) as well as other published reports. (10,11) Our data show that the CpG island methylation of miRNAs is common in NSCLC, and that the methylation of multiple miR-NA loci is associated with an advanced T status as well as the progression-free survival (PFS) of patients with NSCLC. Materials and MethodsPatients. We collected cancer tissues and normal lung tissues from NSCLC patients who underwent surgical resection at the University of Tokyo Hosp...

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Section: Discussioncontrasting

confidence: 65%

CpG island methylation of microRNAs is associated with tumor size and recurrence of non‐small‐cell lung cancer

Kitano

Watanabe²,

Emoto³

et al. 2011

Cancer Science

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“…RASSF1A inactivation is associated with progression of the neoplasm and worsening of prognosis. Other suppressor genes characterized by increased methylation of promoter regions in lung cancer are: FHIT [28], CDH13 [33,34], KLK10 [33], EFEMP1 [33], SFRP1 [33], RARβ [33,34], APC [33], and DAPK [35]. Silencing these genes causes a decrease in the amount of synthesized protein to a level insufficient for normal cell cycle regulation [36].…”

Section: Epigeneticsmentioning

confidence: 99%

EXPERIMENTAL CARDIOVASCULAR AND LUNG RESEARCH From mutation to methylation – molecular markers in lung cancer

Lewandowska¹,

Grębicka²,

Chrustek³

et al. 2013

kitp

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StreszczenieRak płuca jest najczęstszym oraz najgorzej rokującym nowotworem złośliwym na świecie oraz w Polsce. Na świecie z jego powodu umiera ok. 2 mln osób rocznie, w Polsce odnotowuje się ok. 14,5 tys. zachorowań u mężczyzn, a u kobiet rak płuca zajmuje trzecie miejsce z ponad 6 tys. zachorowań. Przyczyną powstawania raka płuca u 85% mężczyzn i u 47% kobiet jest palenie papierosów. W ciągu ostatnich lat nastąpił ogromny postęp wysokozaawansowanych i wysokorozdzielczych technologii z zakresu biologii molekularnej, takich jak sekwencjonowanie nowej generacji, mikromacierze, spektrometria mas, co przyczyniło się do rozwoju badań z zakresu genomiki, transkryptomiki i epigenetyki w raku płuca. Coraz szybsze wdraża-nie wyników tych dyscyplin pozwala na wykorzystanie analiz somatycznych mutacji punktowych czy translokacji do molekularnej diagnostyki onkologicznej, a tym samym na personalizację leczenia pacjentów z niedrobnokomórkowym rakiem płuca. Niestety, nadal brakuje zarówno markerów predykcyjnych, jak i prognostycznych, które pomogłyby w wykrywaniu raka płuca we wczesnym etapie rozwoju choroby. Słowa kluczowe: markery molekularne, personalizowana onkologia, diagnostyka molekularna. Kardiochirurgia i Torakochirurgia Polska 2013; 10 (2) 148 EXPERIMENTAL CARDIOVASCULAR AND LUNG RESEARCH AbstractLung cancer is one of the most common types of malignant neoplasms in Poland and in the world, and is associated with the worst prognosis. Within recent years, significant progress has been made when it comes to high-throughput and highresolution technologies in the field of molecular biology, i.e. next-generation sequencing, microarrays, and mass spectrometry, which contributed to the development of research in the fields of genomics, transcriptomics and epigenetics in lung cancer. Implementing the results achieved by these disciplines quickly allows for the analysis of somatic point mutations or translocations to be used in molecular cancer diagnostics, and, thus, for the personalization of treatment for patients with non-small cell lung cancer (NSCLC). Unfortunately, certain markers and prognostic predictors that could facilitate the detection of lung cancer in its early stages are yet to be found.

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“…DNA methylation is one of the most common epigenetic mechanisms studied, including genome-wide hypomethylation and site-specific CpG island hypermethylation. [9][10][11] Methylation profiles at specific CpG islands of tumor suppressor genes have been described for various cancers and are considered promising markers for early detection, tumor classification and chemotherapy response. [9][10][11][12] The transcriptional inactivation caused by promoter hypermethylation affects genes involved in important cellular pathways, and has been suggested as a diagnostic tool for PE.…”

Section: Prognostic Value Of Aberrant Hypermethylation In Pleural Effmentioning

confidence: 99%

“…[9][10][11] Methylation profiles at specific CpG islands of tumor suppressor genes have been described for various cancers and are considered promising markers for early detection, tumor classification and chemotherapy response. [9][10][11][12] The transcriptional inactivation caused by promoter hypermethylation affects genes involved in important cellular pathways, and has been suggested as a diagnostic tool for PE. [13][14][15][16] However, there is practically no evidence of its relation with prognosis in patients with MPE.…”

Section: Prognostic Value Of Aberrant Hypermethylation In Pleural Effmentioning

confidence: 99%

Prognostic value of aberrant hypermethylation in pleural effusion of lung adenocarcinoma

Botana-Rial

Chiara

Valverde

et al. 2012

Cancer Biology & Therapy

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Methylation of multiple genes as a candidate biomarker in non-small cell lung cancer

Cited by 188 publications

References 40 publications

CpG island methylation of microRNAs is associated with tumor size and recurrence of non‐small‐cell lung cancer

CpG island methylation of microRNAs is associated with tumor size and recurrence of non‐small‐cell lung cancer

EXPERIMENTAL CARDIOVASCULAR AND LUNG RESEARCH From mutation to methylation – molecular markers in lung cancer

Prognostic value of aberrant hypermethylation in pleural effusion of lung adenocarcinoma

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