Dataset Information

CpG island methylator phenotype and prognosis of colorectal cancer in Northeast China.

ABSTRACT: To investigate the association between CpG island methylator phenotype (CIMP) and the overall survival of sporadic colorectal cancer (CRC) in Northeast China.282 sporadic CRC patients were recruited in this study. We selected MLH1, MGMT, p16, APC, MINT1, MINT31, and RUNX3 as the CIMP panel markers. The promoter methylation was assessed by methylation sensitive high resolution melting (MS-HRM). Proportional hazards-regression models were fitted with computing hazard ratios (HR) and the corresponding 95% confidence intervals (95% CI).12.77% (36/282) of patients were CIMP-0, 74.1% (209/282) of patients were CIMP-L, and 13.12% (37/282) of patients were CIMP-H. The five-year survival of the 282 CRC patients was 58%. There was significant association between APC gene promoter methylation and CRC overall survival (HR = 1.61; 95% CI: 1.05-2.46; P = 0.03). CIMP-H was significantly associated with worse prognosis compared to CIMP-0 (HR = 3.06; 95% CI: 1.19-7.89; P = 0.02) and CIMP-L (HR = 1.97; 95% CI: 1.11-3.48; P = 0.02), respectively. While comparing with the combine of CIMP-L and CIMP-0 (CIMP-L/0), CIMP-H also presented a worse prognosis (HR = 2.31; 95% CI: 1.02-5.24; P = 0.04).CIMP-H may be a predictor of a poor prognosis of CRC in Northeast China patients.

SUBMITTER: Li X

PROVIDER: S-EPMC4163374 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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CpG island methylator phenotype and prognosis of colorectal cancer in Northeast China.

Li Xia X Hu Fulan F Wang Yibaina Y Yao Xiaoping X Zhang Zuoming Z Wang Fan F Sun Guizhi G Cui Bin-Bin BB Dong Xinshu X Zhao Yashuang Y

BioMed research international 20140828

<h4>Purpose</h4>To investigate the association between CpG island methylator phenotype (CIMP) and the overall survival of sporadic colorectal cancer (CRC) in Northeast China.<h4>Methods</h4>282 sporadic CRC patients were recruited in this study. We selected MLH1, MGMT, p16, APC, MINT1, MINT31, and RUNX3 as the CIMP panel markers. The promoter methylation was assessed by methylation sensitive high resolution melting (MS-HRM). Proportional hazards-regression models were fitted with computing hazar ...[more]

PMID: 25243122

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Project description:We analyzed 28 fresh frozen samples from pure SCLC patients and 13 noncancerous lung tissues, using the Illumina Infinium 27k Human DNA methylation Beadchip v1.2 Background: Small cell lung cancer (SCLC) accounts for 13-15% of new lung cancer cases in worldwide and has the poor therapeutic outcomes with a median survival of just over one year. A CpG island methylate phenotype (CIMP) is well known as a methylator phenotype with characteristic promoter DNA methylation alterations, in colorectal cancers, glioblastoma and breast cancers, although there has been no report about any CIMP of SCLC. We investigated whether DNA methylation profiles can provide useful molecular subtyping of SCLC in terms of etiology and prognosis of SCLC. Results: We selected a total of 1741 most differentially methylated CpG sites (s.d. > 0.20) across the 28 SCLC tumor tissues in each DNA methylation platform, after an elimination of the probes related with the X- and Y- chromosome. Unsupervised hierarchical clustering of methylation data from SCLC samples reveals two major subgroups with different prognosis: the 5 years disease-free interval (DFI) rate of patients in cluster 1 (11.1%) was lower than that of patients in cluster 2 (61.57%) (p = 0.001). By multivariate analysis for DFI, both postoperative chemotherapy and cluster 1 were a significant prognostic factor (p = 0.002 and 0.002; respectively). Next, among 1220 genes with methylation and expression data both available, the CpG sites were ranked on the basis of the spearman’s correlation coefficient between cluster 1 and cluster 2 into an ascending order. Finally, we identified that fifty-five CpG sites were nagetively correlated and found that apoptosis pathway was a most differentially expressed. Conclusion: By comprehensive DNA methylation profiling, two distinct subgroups with different molecular and clinical phenotype were identified to evoke a CIMP of SCLC. We found some promoter markers in the apoptosis pathway could make a difference between the two groups, and we hope that our data can contribute to provide a useful resource for the construction of therapeutic strategy and the development of a new chemotherapeutic agent.

Dataset Information

CpG island methylator phenotype and prognosis of colorectal cancer in Northeast China.

Publications

CpG island methylator phenotype and prognosis of colorectal cancer in Northeast China.

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