Methylation status of IGF2 DMR and LINE1 in leukocyte DNA provides distinct clinicopathological features of gastric cancer patients

Abstract

DNA methylation of leukocyte DNA has been proposed to be a biomarker for cancer that can be used to target patients for appropriate clinical implementation. We investigated IGF2 DMR and LINE1 methylation in the leukocyte DNA and their association with clinicopathological features and prognosis of gastric cancer (GC) patients. Methylation status of IGF2 DMR and LINE1 in the leukocyte DNA was quantified using bisulfite pyrosequencing in 207 GC patients. Methylation of both IGF2 DMR and the LINE1 was significantly higher in the undifferentiated histologic type compared to the differentiated histologic type (both P = 0.0002). Hypermethylation of both the IGF2 DMR and the LINE1 was associated with more aggressive features of GC such as advanced stage (IGF2 DMR, P = 0.0002; LINE1, P < 0.0001), lymphatic invasion positive (IGF2 DMR, P = 0.004; LINE1, P = 0.002), venous invasion positive (IGF2 DMR, LINE1, both P = 0.03), lymph node metastasis positive (IGF2 DMR, P = 0.01; LINE1, P = 0.001), peritoneal dissemination positive (IGF2 DMR, P = 0.04; LINE1, P = 0.002), liver metastasis positive (IGF2 DMR, P = 0.008; LINE1, P = 0.001), and other distant metastasis positive (IGF2 DMR, P = 0.04). Our data suggest that high LINE1 and IGF2 DMR methylation status would be a phenomenon that is observed with the progression of GC, supporting their potential utility as a biomarker in GC patients.

The Neglected Insulin: IGF-II, a Metabolic Regulator with Implications for Diabetes, Obesity, and Cancer

“…This evidence also indicates that activation of the IGF-II locus may promote EMT [191] that could then facilitate tumor invasion and metastasis. This is consistent with reports that IGF-II is associated with progression and prognosis [193,194,195,196]. A further implication of the reactivated developmental program is related to the splice variant of the insulin receptor, IR-A, which was originally reported to be highly expressed in fetal and cancer cells [77].…”

WITHDRAWN: Assessment of DOK7 and SPDEF as Potential Epigenetic Biomarkers in Whole Blood of Patients with Gastric Adenocarcinoma and Intestinal Metaplasia

“…If selected DNA methylation markers are consistent and replicable, they can be utilized in clinical practices. Since blood is a convenient tissue in noninvasive cancer assays, evaluation of cancer biomarker is under intensive attention in DNA extracted from WBC [21].…”

DNA methylation profiling to predict overall survival risk in gastric cancer: development and validation of a nomogram to optimize clinical management

“…Tanaka Tomokazu and colleagues found that low expression of Trefoil factor 1 (TFF1) was relevant to poor survival in gastric cancer patients who were treated by surgery alone, while the expression of TFF1 was silenced by DNA methylation and was also associated with tumor invasion [31]. Other studies also showed that high methylation status of IGF2 and LINE1 was associated with invasion of gastric cancer [32] and hypermethylation of GFRA3 promoter may predict poor overall survival in gastric cancer patients who underwent surgery [33]. Besides, Li et al reported that integrative analysis of DNA methylation and gene expression identified a six epigenetic driver signature for predicting prognosis in hepatocellular carcinoma [34].…”