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甲基化介导的基因沉默作为胃癌生物标志物的综述

Methylation-mediated gene silencing as biomarkers of gastric cancer: a review.

作者信息

Nakamura Jun, Tanaka Tomokazu, Kitajima Yoshihiko, Noshiro Hirokazu, Miyazaki Kohji

机构信息

Jun Nakamura, Tomokazu Tanaka, Yoshihiko Kitajima, Hirokazu Noshiro, Kohji Miyazaki, Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan.

出版信息

World J Gastroenterol. 2014 Sep 14;20(34):11991-2006. doi: 10.3748/wjg.v20.i34.11991.

Abstract

Despite a decline in the overall incidence of gastric cancer (GC), the disease remains the second most common cause of cancer-related death worldwide and is thus a significant global health problem. The best means of improving the survival of GC patients is to screen for and treat early lesions. However, GC is often diagnosed at an advanced stage and is associated with a poor prognosis. Current diagnostic and therapeutic strategies have not been successful in decreasing the global burden of the disease; therefore, the identification of reliable biomarkers for an early diagnosis, predictive markers of recurrence and survival and markers of drug sensitivity and/or resistance is urgently needed. The initiation and progression of GC depends not only on genetic alterations but also epigenetic changes, such as DNA methylation and histone modification. Aberrant DNA methylation is the most well-defined epigenetic change in human cancers and is associated with inappropriate gene silencing. Therefore, an increasing number of genes methylated at the promoter region have been targeted as possible biomarkers for different purposes, including early detection, classification, the assessment of the tumor prognosis, the development of therapeutic strategies and patient follow-up. This review article summarizes the current understanding and recent evidence regarding DNA methylation markers in GC with a focus on the clinical potential of these markers.

摘要

尽管全球胃癌(GC)的总体发病率有所下降,但该疾病仍是全球癌症相关死亡的第二大常见原因,因此是一个重大的全球健康问题。提高GC患者生存率的最佳方法是筛查和治疗早期病变。然而,GC往往在晚期才被诊断出来,且预后较差。目前的诊断和治疗策略未能成功减轻该疾病的全球负担;因此,迫切需要鉴定用于早期诊断的可靠生物标志物、复发和生存的预测标志物以及药物敏感性和/或耐药性标志物。GC的发生和发展不仅取决于基因改变,还取决于表观遗传变化,如DNA甲基化和组蛋白修饰。异常DNA甲基化是人类癌症中最明确的表观遗传变化,与不适当的基因沉默有关。因此,越来越多在启动子区域甲基化的基因已被作为不同目的的可能生物标志物,包括早期检测、分类、肿瘤预后评估、治疗策略制定和患者随访。这篇综述文章总结了目前对GC中DNA甲基化标志物的认识和最新证据,重点关注这些标志物的临床潜力。

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