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
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Mentions: Next, to identify SCLC subgroups, we used the 1741 probes with an SD of mean β‐value in tumor tissues >0.2 on each site and performed both the unsupervised hierarchical clustering (Fig. 3a) and the NMF (Fig. 3b). We identified two clusters with different methylation levels: Cluster 1 (n = 9) and Cluster 2 (n = 19). As shown in Figure 3(a,b), the two clusters created by both the methods were exactly the same, implying that the clusters were very robust. Cluster 1 tumors were identified as SCLC CIMP and Cluster 2 was non‐CIMP, because the CpG islands of Cluster 1 tumors were significantly hypermethylated as compared with Cluster 2 tumors (Fig. 4).
Affiliation: Division of Pathology, The Cancer Institute, Department of Pathology, The Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan.