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与 和 甲基化状态相关的多态性与台湾结直肠癌的不良预后相关。

polymorphisms with and methylation status are associated with poor prognosis of colorectal cancer in Taiwan.

机构信息

Division of Colorectal Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan.

School of Public Health, National Defense Medical Center, Taipei 114, Taiwan.

出版信息

World J Gastroenterol. 2021 Sep 14;27(34):5737-5752. doi: 10.3748/wjg.v27.i34.5737.

Abstract

BACKGROUND

Identifying novel colorectal cancer (CRC) prognostic biomarkers is crucial to helping clinicians make appropriate therapy decisions. Melatonin plays a major role in managing the circadian rhythm and exerts oncostatic effects on different kinds of tumours.

AIM

To explore the relationship between single-nucleotide polymorphism (SNPs) combined with gene hypermethylation and CRC prognosis.

METHODS

A total of 94 CRC tumour tissues were investigated. Genotyping for the four SNPs (rs1387153, rs2166706, rs10830963, and rs1447352) was performed using multiplex polymerase chain reaction. The relationships between the SNPs and CRC 5-year overall survival (OS) was assessed by calculating hazard ratios with 95%CIs.

RESULTS

All SNPs (rs1387153, rs2166706, rs10830963, and rs1447352) were correlated with decreased 5-year OS. In stratified analysis, rs1387153, rs10830963, and rs1447352 risk genotype combined with CDKN2A and MGMT methylation status were associated with 5-year OS. A strong cumulative effect of the four polymorphisms on CRC prognosis was observed. Four haplotypes of SNPs were also associated with the 5-year OS. SNPs combined with and gene methylation status could be used to predict shorter CRC survival.

CONCLUSION

The novel genetic biomarkers combined with epigenetic biomarkers may be predictive tool for CRC prognosis and thus could be used to individualise treatment for patients with CRC.

摘要

背景

识别新的结直肠癌(CRC)预后生物标志物对于帮助临床医生做出适当的治疗决策至关重要。褪黑素在调节昼夜节律方面发挥着重要作用,并对不同类型的肿瘤产生抗肿瘤作用。

目的

探讨单核苷酸多态性(SNP)与基因甲基化联合与 CRC 预后的关系。

方法

共检测了 94 例 CRC 肿瘤组织。采用多重聚合酶链反应对四个 SNP(rs1387153、rs2166706、rs10830963 和 rs1447352)进行基因分型。通过计算风险比及其 95%置信区间评估 SNP 与 CRC 5 年总生存率(OS)之间的关系。

结果

所有 SNP(rs1387153、rs2166706、rs10830963 和 rs1447352)均与降低 5 年 OS 相关。在分层分析中,rs1387153、rs10830963 和 rs1447352 风险基因型与 CDKN2A 和 MGMT 甲基化状态结合与 5 年 OS 相关。四种多态性对 CRC 预后的累积效应较强。四个 SNP 的单倍型也与 5 年 OS 相关。SNP 与和基因甲基化状态相结合可用于预测 CRC 生存时间较短。

结论

新型遗传生物标志物与表观遗传生物标志物相结合可能是 CRC 预后的预测工具,从而可以用于对 CRC 患者进行个体化治疗。

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