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Cancer Sci. 2016 Mar;107(3):320-5. doi: 10.1111/cas.12876. Epub 2016 Feb 19.

Prognostic significance of CpG island methylator phenotype in surgically resected small cell lung carcinoma.

Author information

1
Division of Pathology, The Cancer Institute, Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
2
Department of Thoracic Surgery, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
3
Genome Science Division, Research Center for Advanced Science and Technology, The University of Tokyo, Tokyo, Japan.
4
Thoracic Surgical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.
5
Thoracic Medical Oncology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.

Abstract

Methylation is closely involved in the development of various carcinomas. However, few datasets are available for small cell lung cancer (SCLC) due to the scarcity of fresh tumor samples. The aim of the present study is to clarify relationships between clinicopathological features and results of the comprehensive genome-wide methylation profile of SCLC. We investigated the genome-wide DNA methylation status of 28 tumor and 13 normal lung tissues, and gene expression profiling of 25 SCLC tissues. Following unsupervised hierarchical clustering and non-negative matrix factorization, gene ontology analysis was performed. Clustering of SCLC led to the important identification of a CpG island methylator phenotype (CIMP) of the tumor, with a significantly poorer prognosis (P = 0.002). Multivariate analyses revealed that postoperative chemotherapy and non-CIMP were significantly good prognostic factors. Ontology analyses suggested that the extrinsic apoptosis pathway was suppressed, including TNFRSF1A, TNFRSF10A and TRADD in CIMP tumors. Here we revealed that CIMP was an important prognostic factor for resected SCLC. Delineation of this phenotype may also be useful for the development of novel apoptosis-related chemotherapeutic agents for treatment of the aggressive tumor.

KEYWORDS:

CpG island methylator phenotype; epigenetics; lung cancer; methylation; small cell lung cancer

PMID:
26748784
PMCID:
PMC4814245
DOI:
10.1111/cas.12876
[Indexed for MEDLINE]
Free PMC Article

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