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启动子CpG岛高甲基化与II期结直肠癌患者的不良预后相关。

promoter CpG island hypermethylation is associated with poor prognosis in patients with stage II colorectal cancer.

作者信息

Wang Chuntao, Liu Yanliang, Guo Wenyi, Zhu Xu, Ahuja Nita, Fu Tao

机构信息

Department of Gastrointestinal Surgery II, Key Laboratory of Hubei Province for Digestive System Disease, Renmin Hospital, Wuhan University, Wuhan, People's Republic of China.

Department of Surgery, Yale School of Medicine, New Haven, CT, USA.

出版信息

Cancer Manag Res. 2019 Aug 5;11:7337-7343. doi: 10.2147/CMAR.S206731. eCollection 2019.

Abstract

BACKGROUND

The methylation of microtubule-associated protein tau () was first described in patients with Alzheimer's disease. In this study, we aim to determine if promoter CpG island is hypermethylated and whether this signature could work as a prognostic marker for patients with stage II colorectal cancer (CRC).

METHODS

methylation level and CpG island methylator phenotype (CIMP) status were examined. The prognostic value of methylation was analyzed using Cox regression analysis.

RESULTS

Amongst stage II CRC patients (n=107), hypermethylation of promoter CpG island was seen in 23.4% of them. methylation was much more frequent in patients with age ≥60 compared to age <60 (0.001). were preferentially methylated among proximal colon tumors or CIMP high tumors (both 0.001). Five-year overall survival (OS) rates were 57.1% and 79.4% for patients with and without hypermethylation, respectively, HR=2.33 (95% CI, 1.19-4.57; 0.014). hypermethylation remained an important prognostic variable for OS in multivariate analysis with a HR of 2.29 (95% CI, 1.01-5.18; 0.047).

CONCLUSION

Our findings suggest that is frequently methylated and hypermethylation is associated with worse prognosis in patients with stage II CRC.

摘要

背景

微管相关蛋白tau()的甲基化最早在阿尔茨海默病患者中被描述。在本研究中,我们旨在确定tau启动子CpG岛是否发生高甲基化,以及这种特征是否可作为II期结直肠癌(CRC)患者的预后标志物。

方法

检测tau甲基化水平和CpG岛甲基化表型(CIMP)状态。使用Cox回归分析评估tau甲基化的预后价值。

结果

在II期CRC患者(n = 107)中,23.4%的患者存在tau启动子CpG岛的高甲基化。与年龄<60岁的患者相比,年龄≥60岁的患者中tau甲基化更为常见(P = 0.001)。在近端结肠肿瘤或CIMP高的肿瘤中,tau优先发生甲基化(均为P = 0.001)。tau高甲基化和未发生高甲基化的患者5年总生存率(OS)分别为57.1%和79.4%,HR = 2.33(95%CI,1.19 - 4.57;P = 0.014)。在多变量分析中,tau高甲基化仍然是OS的重要预后变量,HR为2.29(95%CI,1.01 - 5.18;P = 0.047)。

结论

我们的研究结果表明,tau在II期CRC患者中经常发生甲基化,且高甲基化与预后较差相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3dc4/6689138/de5ceea6c1f1/CMAR-11-7337-g0001.jpg

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