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

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

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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.

Original languageEnglish
Pages (from-to)215-220
Number of pages6
JournalClinical and Experimental Medicine
Volume18
Issue number2
DOIs
Publication statusPublished - 01-05-2018

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Methylation
Stomach Neoplasms
Leukocytes
DNA
Neoplasm Metastasis
Biomarkers
Tumor Biomarkers
Liver
DNA Methylation
Association reactions
Lymph Nodes

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Tahara, Tomomitsu ; Tahara, Sayumi ; Horiguchi, Noriyuki ; Kawamura, Tomohiko ; Okubo, Masaaki ; Yamada, Hyuga ; Yoshida, Dai ; Ohmori, Takafumi ; Maeda, Kohei ; Komura, Naruomi ; Ikuno, Hirokazu ; Jodai, Yasutaka ; Kamano, Toshiaki ; Nagasaka, Mitsuo ; Nakagawa, Yoshihito ; Tsukamoto, Tetsuya ; Urano, Makoto ; Shibata, Tomoyuki ; Kuroda, Makoto ; Ohmiya, Naoki. / Methylation status of IGF2 DMR and LINE1 in leukocyte DNA provides distinct clinicopathological features of gastric cancer patients. In: Clinical and Experimental Medicine. 2018 ; Vol. 18, No. 2. pp. 215-220.
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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.",
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Tahara, T, Tahara, S, Horiguchi, N, Kawamura, T, Okubo, M, Yamada, H, Yoshida, D, Ohmori, T, Maeda, K, Komura, N, Ikuno, H, Jodai, Y, Kamano, T, Nagasaka, M, Nakagawa, Y, Tsukamoto, T, Urano, M, Shibata, T, Kuroda, M & Ohmiya, N 2018, 'Methylation status of IGF2 DMR and LINE1 in leukocyte DNA provides distinct clinicopathological features of gastric cancer patients', Clinical and Experimental Medicine, vol. 18, no. 2, pp. 215-220. https://doi.org/10.1007/s10238-017-0471-4

Methylation status of IGF2 DMR and LINE1 in leukocyte DNA provides distinct clinicopathological features of gastric cancer patients. / Tahara, Tomomitsu; Tahara, Sayumi; Horiguchi, Noriyuki; Kawamura, Tomohiko; Okubo, Masaaki; Yamada, Hyuga; Yoshida, Dai; Ohmori, Takafumi; Maeda, Kohei; Komura, Naruomi; Ikuno, Hirokazu; Jodai, Yasutaka; Kamano, Toshiaki; Nagasaka, Mitsuo; Nakagawa, Yoshihito; Tsukamoto, Tetsuya; Urano, Makoto; Shibata, Tomoyuki; Kuroda, Makoto; Ohmiya, Naoki.

In: Clinical and Experimental Medicine, Vol. 18, No. 2, 01.05.2018, p. 215-220.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Methylation status of IGF2 DMR and LINE1 in leukocyte DNA provides distinct clinicopathological features of gastric cancer patients

AU - Tahara, Tomomitsu

AU - Tahara, Sayumi

AU - Horiguchi, Noriyuki

AU - Kawamura, Tomohiko

AU - Okubo, Masaaki

AU - Yamada, Hyuga

AU - Yoshida, Dai

AU - Ohmori, Takafumi

AU - Maeda, Kohei

AU - Komura, Naruomi

AU - Ikuno, Hirokazu

AU - Jodai, Yasutaka

AU - Kamano, Toshiaki

AU - Nagasaka, Mitsuo

AU - Nakagawa, Yoshihito

AU - Tsukamoto, Tetsuya

AU - Urano, Makoto

AU - Shibata, Tomoyuki

AU - Kuroda, Makoto

AU - Ohmiya, Naoki

PY - 2018/5/1

Y1 - 2018/5/1

N2 - 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.

AB - 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.

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