Tomomitsu Tahara, Sayumi Tahara, Noriyuki Horiguchi, Tomohiko Kawamura, Masaaki Okubo, Hyuga Yamada, Dai Yoshida, Takafumi Ohmori, Kohei Maeda, Naruomi Komura, Hirokazu Ikuno, Yasutaka Jodai, Toshiaki Kamano, Mitsuo Nagasaka, Yoshihito Nakagawa, Tetsuya Tsukamoto, Makoto Urano, Tomoyuki Shibata, Makoto Kuroda, Naoki Ohmiya
Clinical and Experimental Medicine 18(2) 215-220 2018年5月1日 査読有り
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.