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

• Published in: Cancer science 2016-03, Vol.107 (3), p.320-325
• Main Authors: Saito, Yuichi, Nagae, Genta, Motoi, Noriko, Miyauchi, Eisaku, Ninomiya, Hironori, Uehara, Hirofumi, Mun, Mingyon, Okumura, Sakae, Ohyanagi, Fumiyoshi, Nishio, Makoto, Satoh, Yukitoshi, Aburatani, Hiroyuki, Ishikawa, Yuichi
• Format: Article
• Language: English
• Subjects: Aged; Apoptosis; Apoptosis Regulatory Proteins - genetics; Apoptosis Regulatory Proteins - metabolism; Cancer therapies; Carcinoma; Chemotherapy; CpG island methylator phenotype; CpG Islands; Datasets; Deoxyribonucleic acid; Disease-Free Survival; DNA; DNA Methylation; Epigenetics; Female; Gene expression; Gene Expression Regulation, Neoplastic; Gene Ontology; Genomes; Humans; Kaplan-Meier Estimate; Lung cancer; Lung carcinoma; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - mortality; Lung Neoplasms - surgery; Male; Medical research; methylation; Middle Aged; Multivariate Analysis; Original; Phenotype; Phenotypes; Prognosis; small cell lung cancer; Small cell lung carcinoma; Small Cell Lung Carcinoma - genetics; Small Cell Lung Carcinoma - metabolism; Small Cell Lung Carcinoma - mortality; Small Cell Lung Carcinoma - surgery; Software; Studies; Survival analysis; Transcriptome; Tumors; Values
• ISSN: 1347-9032; 1349-7006
• DOI: 10.1111/cas.12876

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. We investigated genome‐wide DNA methylation status of 28 tumor and 13 normal lung tissues, and gene expression profiling of 25 SCLC tissues. 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 the non‐CIMP were significantly good prognostic factors.