Prognostic significance of CpG island methylator phenotype in surgically resected small cell lung carcinoma.
Bottom Line: 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.Delineation of this phenotype may also be useful for the development of novel apoptosis-related chemotherapeutic agents for treatment of the aggressive tumor.
Affiliation: Division of Pathology, The Cancer Institute, Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.Show MeSH
Related in: MedlinePlus
Mentions: Using the 147 genes mentioned above, we verified this gene set to be discriminable between malignant and benign lung tissues. The DNA methylation datasets of tumors and normal lung tissues reported previously17 were used as an independent validation set: GSE35341 downloaded from NCBI GEO data repository http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE35341. We employed 18 SCLC tumor tissues (T1–T18) and five normal lung tissues (N1–N5) from the series to confirm our results. To apply the probes of the Illumina Infinium HumanMethylation27 microarray to that of the NimbleGen tiling arrays, all sequences of each probe set were compared and adjusted approximately. According to the result of clustering analysis in GSE35341, the 147 probes were able to distinguish cancerous from non‐cancerous specimens sufficiently: 17 out of 18 SCLC were correctly classified as “tumor” and 4 out of 5 normal lung tissues were correctly classified as “healthy” (Fig. 2).
Affiliation: Division of Pathology, The Cancer Institute, Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.