Tumors with unmethylated MLH1 and the CpG island methylator phenotype are associated with a poor prognosis in stage II colorectal cancer patients.
Tumors with unmethylated MLH1 and the CpG island methylator phenotype are associated with a poor prognosis in stage II colorectal cancer patients.
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DOI：
10.18632/oncotarget.13441
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发表时间：
2016-12-27
期刊：
影响因子：
--
通讯作者：
Ahuja N
中科院分区：
文献类型：
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作者：
Fu T;Liu Y;Li K;Wan W;Pappou EP;Iacobuzio-Donahue CA;Kerner Z;Baylin SB;Wolfgang CL;Ahuja N
我们之前基于 CpG 岛甲基化表型 (CIMP) 和 MLH1 甲基化状态的组合开发了一种新型十二指肠腺癌肿瘤亚型分类模型。在这里，我们测试了该模型在 II 期结直肠癌 (CRC) 患者中的预后价值。肿瘤被分配至 CIMP+/MLH1-未甲基化 (MLH1-U)、CIMP+/MLH1-甲基化 (MLH1-M)、CIMP-/MLH1-U 或 CIMP-/MLH1-M 组。四个患者亚组的年龄、肿瘤位置、淋巴血管侵犯和粘蛋白产生不同，CIMP+/MLH1-U 肿瘤更有可能发生淋巴管侵犯和粘蛋白产生。 Kaplan-Meier 分析揭示了四组之间无病生存期 (DFS) 和总生存期 (OS) 的差异。在多变量分析中，CIMP/MLH1 甲基化状态可预测 DFS 和 OS，并且 CIMP+/MLH1-U II 期 CRC 患者的 DFS 和 OS 最短。这些结果表明，基于 CIMP 和 MLH1 甲基化状态组合的肿瘤亚型分类对于 II 期 CRC 患者具有重要意义，并且 CIMP+/MLH1-U 肿瘤表现出侵袭性特征并与不良临床结果相关。
We previously developed a novel tumor subtype classification model for duodenal adenocarcinomas based on a combination of the CpG island methylator phenotype (CIMP) and MLH1 methylation status. Here, we tested the prognostic value of this model in stage II colorectal cancer (CRC) patients. Tumors were assigned to CIMP+/MLH1-unmethylated (MLH1-U), CIMP+/MLH1-methylated (MLH1-M), CIMP−/MLH1-U, or CIMP−/MLH1-M groups. Age, tumor location, lymphovascular invasion, and mucin production differed among the four patient subgroups, and CIMP+/MLH1-U tumors were more likely to have lymphovascular invasion and mucin production. Kaplan-Meier analyses revealed differences in both disease-free survival (DFS) and overall survival (OS) among the four groups. In a multivariate analysis, CIMP/MLH1 methylation status was predictive of both DFS and OS, and DFS and OS were shortest in CIMP+/MLH1-U stage II CRC patients. These results suggest that tumor subtype classification based on the combination of CIMP and MLH1 methylation status is informative in stage II CRC patients, and that CIMP+/MLH1-U tumors exhibit aggressive features and are associated with poor clinical outcomes.