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World J Gastroenterol. Sep 14, 2014; 20(34): 11991-12006
Published online Sep 14, 2014. doi: 10.3748/wjg.v20.i34.11991
Methylation-mediated gene silencing as biomarkers of gastric cancer: A review
Jun Nakamura, Tomokazu Tanaka, Yoshihiko Kitajima, Hirokazu Noshiro, Kohji Miyazaki
Jun Nakamura, Tomokazu Tanaka, Yoshihiko Kitajima, Hirokazu Noshiro, Kohji Miyazaki, Department of Surgery, Saga University Faculty of Medicine, Saga 849-8501, Japan
Yoshihiko Kitajima, Department of Surgery, National Hospital Organization Higashi-Saga Hospital, 7324 Harakoga, Miyaki Town, Saga 849-0101, Japan
Author contributions: Nakamura J and Tanaka T contributed equally to this work; Nakamura J and Tanaka T wrote the paper; Kitajima Y, Noshiro H and Miyazaki K designed our previous research included in this manuscript.
Correspondence to: Jun Nakamura, MD, PhD, Department of Surgery, Saga University Faculty of Medicine, 5-1-1 Nabeshima, Saga 849-8501, Japan. nakamurj@cc.saga-u.ac.jp
Telephone: +81-952-342349 Fax: +81-952-342019
Received: October 26, 2013
Revised: January 29, 2014
Accepted: April 8, 2014
Published online: September 14, 2014
Processing time: 327 Days and 6.3 Hours
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.

Keywords: Gastric cancer; Methylation; Biomarker; Early detection; Drug sensitivity

Core tip: This article summarizes the current understanding and recent evidence regarding DNA methylation markers in gastric cancer (GC) and includes our previous works. Current diagnostic and therapeutic tools of GC have not been successful in decreasing the global burden of this disease; however, it is promising that the early diagnosis and careful selection of patient subsets prior to initiating chemotherapy is a key factor for improving the outcomes of patients with GC. Methylation biomarkers would be useful for different purposes, including early detection, classification, assessment of the tumor prognosis, the development of therapeutic strategies and patient follow-up.