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Distinct clinical outcomes of two CIMP-positive colorectal cancer subtypes based on a revised CIMP classification system.

ABSTRACT: Colorectal cancer (CRC) is a heterogeneous disease in terms of molecular carcinogenic pathways. Based on recent findings regarding the multiple serrated neoplasia pathway, we revised an eight-marker panel for a new CIMP classification system.1370 patients who received surgical resection for CRCs were classified into three CIMP subtypes (CIMP-N: 0-4 methylated markers, CIMP-P1: 5-6 methylated markers and CIMP-P2: 7-8 methylated markers). Our findings were validated in a separate set of high-risk stage II or stage III CRCs receiving adjuvant fluoropyrimidine plus oxaliplatin (n=950).A total of 1287/62/21 CRCs cases were classified as CIMP-N/CIMP-P1/CIMP-P2, respectively. CIMP-N showed male predominance, distal location, lower T, N category and devoid of BRAF mutation, microsatellite instability (MSI) and MLH1 methylation. CIMP-P1 showed female predominance, proximal location, advanced TNM stage, mild decrease of CK20 and CDX2 expression, mild increase of CK7 expression, BRAF mutation, MSI and MLH1 methylation. CIMP-P2 showed older age, female predominance, proximal location, advanced T category, markedly reduced CK20 and CDX2 expression, rare KRAS mutation, high frequency of CK7 expression, BRAF mutation, MSI and MLH1 methylation. CIMP-N showed better 5-year cancer-specific survival (CSS; HR=0.47; 95% CI: 0.28-0.78) in discovery set and better 5-year relapse-free survival (RFS; HR=0.50; 95% CI: 0.29-0.88) in validation set compared with CIMP-P1. CIMP-P2 showed marginally better 5-year CSS (HR=0.28, 95% CI: 0.07-1.22) in discovery set and marginally better 5-year RFS (HR=0.21, 95% CI: 0.05-0.92) in validation set compared with CIMP-P1.CIMP subtypes classified using our revised system showed different clinical outcomes, demonstrating the heterogeneity of multiple serrated precursors of CIMP-positive CRCs.

SUBMITTER: Bae JM

PROVIDER: S-EPMC5396110 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Distinct clinical outcomes of two CIMP-positive colorectal cancer subtypes based on a revised CIMP classification system.

Bae Jeong Mo JM Kim Jung Ho JH Kwak Yoonjin Y Lee Dae-Won DW Cha Yongjun Y Wen Xianyu X Lee Tae Hun TH Cho Nam-Yun NY Jeong Seung-Yong SY Park Kyu Joo KJ Han Sae Won SW Lee Hye Seung HS Kim Tae-You TY Kang Gyeong Hoon GH

British journal of cancer 20170309 8

<h4>Background</h4>Colorectal cancer (CRC) is a heterogeneous disease in terms of molecular carcinogenic pathways. Based on recent findings regarding the multiple serrated neoplasia pathway, we revised an eight-marker panel for a new CIMP classification system.<h4>Methods</h4>1370 patients who received surgical resection for CRCs were classified into three CIMP subtypes (CIMP-N: 0-4 methylated markers, CIMP-P1: 5-6 methylated markers and CIMP-P2: 7-8 methylated markers). Our findings were valida ...[more]

PMID: 28278514

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Project description:Several Avian paramyxoviruses 1 (synonymous with Newcastle disease virus or NDV, used hereafter) classification systems have been proposed for strain identification and differentiation. These systems pioneered classification efforts; however, they were based on different approaches and lacked objective criteria for the differentiation of isolates. These differences have created discrepancies among systems, rendering discussions and comparisons across studies difficult. Although a system that used objective classification criteria was proposed by Diel and co-workers in 2012, the ample worldwide circulation and constant evolution of NDV, and utilization of only some of the criteria, led to identical naming and/or incorrect assigning of new sub/genotypes. To address these issues, an international consortium of experts was convened to undertake in-depth analyses of NDV genetic diversity. This consortium generated curated, up-to-date, complete fusion gene class I and class II datasets of all known NDV for public use, performed comprehensive phylogenetic neighbor-Joining, maximum-likelihood, Bayesian and nucleotide distance analyses, and compared these inference methods. An updated NDV classification and nomenclature system that incorporates phylogenetic topology, genetic distances, branch support, and epidemiological independence was developed. This new consensus system maintains two NDV classes and existing genotypes, identifies three new class II genotypes, and reduces the number of sub-genotypes. In order to track the ancestry of viruses, a dichotomous naming system for designating sub-genotypes was introduced. In addition, a pilot dataset and sub-trees rooting guidelines for rapid preliminary genotype identification of new isolates are provided. Guidelines for sequence dataset curation and phylogenetic inference, and a detailed comparison between the updated and previous systems are included. To increase the speed of phylogenetic inference and ensure consistency between laboratories, detailed guidelines for the use of a supercomputer are also provided. The proposed unified classification system will facilitate future studies of NDV evolution and epidemiology, and comparison of results obtained across the world.

Dataset Information

Distinct clinical outcomes of two CIMP-positive colorectal cancer subtypes based on a revised CIMP classification system.

Publications

Distinct clinical outcomes of two CIMP-positive colorectal cancer subtypes based on a revised CIMP classification system.

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