In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 393-393
Abstract:
Background: The CpG island methylator phenotype (CIMP) is a distinctive subtype of colon cancers, which leads to the loss of tumor suppressor gene functions by epigenetic regulation. However, molecular characteristics of CIMP+ cancers are not fully understood. Here, we aimed to elucidate the different patterns of gene expression according to the CIMP status. Method: 158 patients with stage III colon cancer were enrolled for the analysis of CIMP status. Pyrosequencing was used to examine the methylation status of 7 CpG island loci (p14, p16, MINT1, MINT2, MINT31, hMLH1, and WNT5a) in DNA extracted from formalin-fixed paraffin-enbedded specimens. Gene expression analyses of the same samples were also performed using a human cDNA microarray to identify molecular signatures. Result: Among the 158 patients, 31 (19.3%) were CIMP+. Microarray results revealed distinctive gene expression profiles between CIMP+ and CIMP- cancers. Among 57 genes which showed significant changes between CIMP+ and CIMP- cancers, Axin2, the canonical Wnt suppressor, displayed the strongest correlation with the CIMP status (p=0.007). Axin2 was downregulated in CIMP+ cancers compared to CIMP- cancers (p=0.005). In terms of disease-free survival (DFS), tumors with low Axin2 expression showed poor prognosis compared to tumors with high Axin2 expression in microsatellite stable (MSS) patients (p=0.038), while there were no significant changes in DFS of microsatellite instable (MSI) patients (p=0.32). These findings indicate the clinical importance of epigenetic silencing of Axin2 and the subsequent activation of Wnt signaling pathway in MSS colon cancer patients. Conclusion: Axin2 is downregulated in CIMP+ stage III colon cancer patients and the consequent decreased expression of Axin2 is a poor prognostic factor for the DFS in MSS patients. Citation Format: Hongjae Jeon, Se Hyun Kim, Kyu Hyun Park, Hei-Cheul Jeung, Nam Kyu Kim, Minkyu Jung, Kang Young Lee, Chan Hee Park, Sun Young Rha, Hyun Cheol Chung, Joong Bae Ahn. Genome-wide molecular characterization of CIMP positive stage III colon cancer using cDNA microarray analysis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 393. doi:10.1158/1538-7445.AM2014-393
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2014-393
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
