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首页> 美国卫生研究院文献>World Journal of Gastroenterology >Comethylation of p16 and MGMT genes in colorectal carcinoma: Correlation with clinicopathological features and prognostic value
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Comethylation of p16 and MGMT genes in colorectal carcinoma: Correlation with clinicopathological features and prognostic value

机译：大肠癌中p16和MGMT基因的共甲基化：与临床病理特征和预后价值的关系

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AIM: To investigate the significance of p16 and O6-methylguanine-DNA methyltransferase (MGMT) genes promoter hypermethylation and K-ras mutations on colorectal tumorigenesis and progression.METHODS: p16 and MGMT methylation status was examined on 47 tumor samples, and K-ras mutational status was examined on 85 tumor samples. For methylation analysis, a methylation specific PCR (MS-PCR) method was used.RESULTS: p16 and MGMT promoter methylation was found in 51% (24/47) and 43% (20/47) of CRCs, respectively, and the K-ras mutation was found in 44% (37/85) of CRCs. Comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease within a two-year period of observation. Only 27% of patients with simultaneous p16 and MGMT methylation showed the detectible occurrence of metastasis and/or death, compared to 67% of patients without double methylation or with no methylation (3/11 vs 22/33, P < 0.05, χ2-test). In addition, p16 and MGMT comethylation showed a trend toward an association with longer survival in patients with CRCs (35.5 ± 6.0 mo vs 23.1 ± 3.2 mo, P = 0.072, Log-rank test). Progression of the disease within a two-year period was observed in 66% of patients carrying the K-ras mutation, compared to only 19% of patients with wild type K-ras (29/44 vs 7/37, P < 0.001, χ2-test). The presence of the K-ras mutation significantly correlated to shortened overall survival (20.0 ± 1.9 mo vs 37.0 ± 1.8 mo, P < 0.001, Log-rank test). The comethylation of p16 and MGMT genes was significantly associated with lower aggressiveness of the disease even when K-ras mutations were included in the analysis as an independent variable.CONCLUSION: Our data suggest that comethylation of promoters of p16 and MGMT genes could have a prognostic value in patients with CRC. Specifically, concurrent methylation of both genes correlates with better prognosis.
机译：目的：探讨p16和O 6 -甲基鸟嘌呤-DNA甲基转移酶（MGMT）基因启动子的超甲基化和K-ras突变在大肠癌发生发展中的意义。 47个肿瘤样品，在85个肿瘤样品上检查了K-ras突变状态。结果：在51％的CRC（24/47）和43％（20/47）的CRC中发现p16和MGMT启动子甲基化。在44％（37/85）的CRC中发现-ras突变。在两年的观察期内，p16和MGMT基因的共甲基化与该疾病的较低侵袭性显着相关。 p27和MGMT甲基化同时发生的患者中只有27％表现出可检测到的转移和/或死亡发生，而没有双重甲基化或没有甲基化的患者中只有67％（3/11 vs 22/33，P <0.05，χ< sup> 2 -test）。此外，p16和 MGMT 甲基化显示出与CRC患者的更长生存时间相关的趋势（35.5±6.0 mo vs 23.1±3.2 mo， P < / em> = 0.072，对数秩检验）。携带K- ras 突变的患者中有66％观察到两年内疾病的进展，而野生型K- ras （29/44 vs 7/37， P <0.001，χ 2 -检验）。 K- ras 突变的存在与总体生存期缩短显着相关（20.0±1.9 mo vs 37.0±1.8 mo， P <0.001，对数秩测试）。即使分析中包括K- ras 突变， p 16和 MGMT 基因的共甲基化也与疾病的较低侵袭性显着相关。结论：我们的数据表明 p 16和 MGMT 基因启动子的共甲基化可能对CRC患者具有预后价值。特别地，两个基因的同时甲基化与更好的预后相关。

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