Abstract
BackgroundGastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancer-related mortality. Lack of prognostic indicators for patient survival hinders GC treatment and survival.Methods and resultsMethylation profile data of patients with GC obtained from The Cancer Genome Atlas (TCGA) database were analyzed to identify methylation sites as biomarkers for GC prognosis. The cohort was divided into training and validation sets. Univariate Cox, LASSO regression,and multivariate Cox analyses revealed a close correlation of a four-DNA methylation signature as a risk score model with the overall survival of patients with GC. The survival between high-risk and low-risk score patients with GC was significantly different. Analyses of receiver operating characteristics revealed a high prognostic accuracy of the four-DNA methylation signature in patients with GC. The subgroup analysis indicated that the accuracy included that for anatomical region, histologic grade, TNM stage, pathological stage, and sex. The GC prognosis based on the four-DNA methylation signature was more precise than that based on known biomarkers.ConclusionsThe four-DNA methylation signature could serve as a novel independent prognostic factor that could be an important tool to predict the prognostic outcome of GC patients. This potential must be verified in a large-scale population cohort study and through basic research studies.
Highlights
Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancerrelated mortality
The four-DNA methylation signature could serve as a novel independent prognostic factor that could be an important tool to predict the prognostic outcome of GC patients
This potential must be verified in a large-scale population cohort study and through basic research studies
Summary
Gastric cancer (GC) is the fifth most frequently diagnosed cancer and the third leading cause of cancerrelated mortality. The tumor-related genes are hypermethylated in precancerous lesions and intestinal metaplasia [17, 18], and inhibiting DNA methylation reduces the incidence of GC in animal models [19, 20], DNA methylation could be used as a biomarker for diagnosis, treatment and prognosis of GC [15, 21]. DNA methylation research has opened a new field in genomics biology by identifying novel biomarkers for several cancers, such as gastrointestinal tumors, breast and lung cancer, malignant melanoma, and other tumors [22,23,24,25,26,27]. Emerging evidence indicates that DNA methylation is closely correlated with the development, invasion, and metastasis of cancer, and could be a valuable prognostic biomarker [14, 24]
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