Comprehensive analysis of IGF2 DMR0 methylation level in esophageal cancer

• Project/Area Number: 24659617
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Single-year Grants
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: BABA Yoshifumi 熊本大学, 大学院生命科学研究部, 講師 (20599708)
• Co-Investigator(Kenkyū-buntansha): SAKAMOTO Yasuo 熊本大学, 医学部附属病院, 特任助教 (00452897) ; ISHIMOTO Takatsugu 熊本大学, 大学院生命科学研究部, 特任助教 (00594889) ; IWAGAMI Shiro 熊本大学, 医学部附属病院, 特任助教 (70530153)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 癌 / トランスレーショナルリサーチ / IGF2 DMR0 / メチル化 / エピジェネティクス / 食道癌 / 予後因子 / pyrosequence

Research Abstract

The methylation level at IGF2 DMR0 is correlated with IGF2 LOI and is a suggested surrogate marker for IGF2 LOI.The IGF2 imprinting status was screened using ApaI polymorphism, and IGF2 protein expression was evaluated by immunohistochemistry with 30 esophageal squamous cell carcinoma tissue specimens. For survival analysis, IGF2 DMR0 methylation was measured using a bisulfite pyrosequencing assay with 216 ESCC tissue specimens. IGF2 LOI cases exhibited lower DMR0 methylation levels than IGF2 non-LOI cases. Among 202 patients eligible for survival analysis,IGF2 DMR0 hypomethylation was significantly associated with higher cancer-specific mortality. The IGF2 DMR0 methylation level in ESCC was associated with IGF2 LOI and IGF2 protein expression.In addition, IGF2 DMR0 hypomethylation was associated with a shorter survival time, suggesting its potential role as a prognostic biomarker.

Research Products

• [Journal Article] IGF2 DMR0 methylation, loss of imprinting, and patient prognosis inesophageal squamous cell carcinoma (2014)
  • Author(s): A. Murata, Y. Baba, M. Watanabe, H. Shigaki, K. Miyake, T. Ishimoto, M. Iwatsuki, S. Iwagami, N. Yoshida, E. Oki, M. Morita, M. Nakao, and H. Baba.
  • Journal Title: Ann. Surg. Oncol. Volume: 21 Issue: 4 Pages: 1166-1174
  • DOI: 10.1245/s10434-013-3414-7
  • Peer Reviewed / Open Access
• [Journal Article] LINE-1 hypomethylation, DNA copy number alterations, and CDK6 amplification in esophageal squamous cell carcinoma (2014)
  • Author(s): Y. Baba, M. Watanabe, A. Murata, H. Shigaki, K. Miyake, T. Ishimoto, M. Iwatsuki, S. Iwagami, N. Yoshida, E. Oki, K. Sakamaki, M. Nakao, and H. Baba.
  • Journal Title: Clin Cancer Res. Volume: 20 Issue: 5 Pages: 1114-1124
  • DOI: 10.1158/1078-0432.ccr-13-1645
  • Peer Reviewed
• [Journal Article] Clinical implications of the LINE-1 methylation levels in patients with gastrointestinal cancer. (2014)
  • Author(s): Baba Y, Murata A, Watanabe M, Baba H.
  • Journal Title: Surg Today Volume: In press
  • Peer Reviewed
• [Journal Article] Clinical implications of the LINE-1 methylation levels in patients with gastrointestinal cancer (2013)
  • Author(s): Baba Y, Murata A, Watanabe M, Baba H
  • Journal Title: Surg Today Volume: (Epub ahead of print) Issue: 10 Pages: 1807-1816
  • DOI: 10.1007/s00595-013-0763-6
  • Peer Reviewed
• [Journal Article] LINE-1 hypomethylation is associated with a poor prognosis among patients with curatively resected esophageal squamous cell carcinoma (2013)
  • Author(s): Iwagami S, Baba Y, Watanabe M, Shigaki H, Miyake K, Ishimoto T, Iwatsuki M, Sakamaki K, Ohashi Y, Baba H
  • Journal Title: Ann Surg Volume: 257(3) Issue: 3 Pages: 449-55
  • DOI: 10.1097/sla.0b013e31826d8602
  • Peer Reviewed
• [Journal Article] Methylation levels of LINE-1 in primary lesion and matched metastatic lesions of colorectal cancer. (2013)
  • Author(s): Murata A, Baba Y, Watanabe M, Shigaki H, Miyake K, Ishimoto T, Iwatsuki M, Iwagami S, Sakamoto Y, Miyamoto Y, Yoshida N, Nosho K, Baba H.
  • Journal Title: Br J Cancer. Volume: 109 Issue: 2 Pages: 408-415
  • DOI: 10.1038/bjc.2013.289
  • Peer Reviewed
• [Journal Article] LINE-1 hypomethylation in gastric cancer, detected by bisulfite pyrosequencing, is associated with poor prognosis. (2013)
  • Author(s): Shigaki H, Baba Y, et al.
  • Journal Title: Gastric Cancer Volume: in press Issue: 4 Pages: 480-487
  • DOI: 10.1007/s10120-012-0209-7
  • NAID: 40019845213
  • Peer Reviewed
• [Journal Article] Aberrant methylation of LINE-1, SLIT2, MAL, and IGFBP7 in non-small cell lung cancer (2013)
  • Author(s): Suzuki M, Shiraishi K, Eguchi A, Ikeda K, Mori T, Yoshimoto K, Ohba Y, Ito Yamada T, Ito T, Baba Y, Baba H
  • Journal Title: Oncol Rep Volume: 29(4) Issue: 4 Pages: 1308-14
  • DOI: 10.3892/or.2013.2266
  • Peer Reviewed
• [Journal Article] Pyrosequencing assay to measure LINE-1 methylation level in esophageal squamous cell carcinoma (2012)
  • Author(s): Iwagami S, Baba Y, Watanabe M, Shigaki H, Miyake K, Ida S, Nagai Y, Ishimoto T, Iwatsuki M, Sakamoto Y, Miyamoto Y, Baba H.
  • Journal Title: Ann Surg Oncol Volume: 19(8) Issue: 8 Pages: 2726-32
  • DOI: 10.1245/s10434-011-2176-3
  • Peer Reviewed
• [Journal Article] LINE-1 hypomethylation in noncancerous esophageal mucosae is associated with smoking history (2012)
  • Author(s): Shigaki H, Baba Y, Watanabe M, Iwagami S, Miyake K, Ishimoto T, Iwatsuki M, Baba H
  • Journal Title: Ann Surg Oncol Volume: 19(13) Issue: 13 Pages: 4238-43
  • DOI: 10.1245/s10434-012-2488-y
  • Peer Reviewed
• [Presentation] 同時性・異時性頭頚部癌を有する食道癌症例におけるLINE-1メチル化レベル (2013)
  • Author(s): 馬場祥史、渡邊雅之、吉田直矢、小澄敬祐、原田和人、村田飛鳥、岩上志朗、辛島龍一、石本崇胤、馬場秀夫
  • Organizer: 第65回日本気管食道学会総会ならびに学術講演会
  • Place of Presentation: 品川プリンスホテル(東京都)
  • Year and Date: 2013-11-01
• [Presentation] 食道扁平上皮癌におけるLINE-1低メチル化とDNAコピー数異常、CDK6増幅の関係 (2013)
  • Author(s): 馬場祥史、渡邊雅之、村田飛鳥、志垣博信、三宅慧輔、石本崇胤、岩槻政晃、岩上志朗、吉田直矢、馬場秀夫
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2013-10-05
• [Presentation] 大腸癌原発巣と転移巣におけるLINE-1メチル化レベルの比較 (2013)
  • Author(s): 村田飛鳥、馬場祥史、渡邊雅之、志垣博信、岩上志朗、坂本快郎、宮本裕士、別府透、馬場秀夫
  • Organizer: 第24回日本消化器癌発生学会
  • Place of Presentation: 石川県立音楽堂
  • Year and Date: 2013-09-06
• [Presentation] 食道癌におけるLINE-1メチル化レベルとDNAコピー数異常の関係 (2013)
  • Author(s): 馬場祥史、渡邊雅之、村田飛鳥、志垣博信、岩上志朗、石本崇胤、岩槻政晃、吉田直矢、馬場秀夫
  • Organizer: 第24回日本消化器癌発生学会
  • Place of Presentation: 石川県立音楽堂
  • Year and Date: 2013-09-05
• [Presentation] 食道扁平上皮癌におけるIGF2 DMR0メチル化レベルと予後の関係 (2013)
  • Author(s): 村田飛鳥、馬場祥史、渡邊雅之、志垣博信、石本崇胤、岩槻政晃、尾崎宣之、岩上志朗、坂本快郎、宮本裕士、吉田直矢、馬場秀夫
  • Organizer: 第113回日本外科学会学術集会
  • Place of Presentation: マリンメッセ福岡
  • Year and Date: 2013-04-13
• [Presentation] Relationship between LINE-1 methylation level, allelic imbalance and PIK3CA mutation in esophageal squamous cell carcinoma (2013)
  • Author(s): Baba Y, Watanabe M, Murata A, Shigaki H, Iwagami S, Iwatsuki M, Ishimoto T, Baba H
  • Organizer: AACR Annual Meeting 2013
  • Place of Presentation: Washington, DC, USA
  • Year and Date: 2013-04-09
• [Presentation] Methylation levels of LINE-1 in primary lesion and matched metastatic lesions of colorectal cancer (2013)
  • Author(s): Murata A, Baba Y, Watanabe M, Shigaki H, Iwagami S, Sakamoto Y, Miyamoto Y, Baba H
  • Organizer: AACR Annual Meeting 2013
  • Place of Presentation: Washington, DC, USA
  • Year and Date: 2013-04-09
• [Presentation] Hypomethylation of the IGF2 DMR0 in Esophageal Squamous Cell Carcinoma, Detected by Bisulfite Pyrosequencing, is Associated with Poor Prognosis (2013)
  • Author(s): Murata A, Baba Y, Watanabe M, Shigaki H, Miyake K, Ozaki N, Ishimoto T, Iwatsuki M, Iwagami S, Sakamoto Y, Miyamoto Y, Yoshida N, Baba H
  • Organizer: 9th AACR-Japanese Cancer Association Joint Conference (AACR-JCA)
  • Place of Presentation: Hyatt Regency Maui, Hawaii
  • Year and Date: 2013-02-23
• [Presentation] Clinical and prognostic significance of LINE-1metastases from cororectal cancer (2013)
  • Author(s): Baba Y, Watanabe M, Murata A, Shigaki H, Iwagami S, Sakamoto Y, Miyamoto Y, Beppu T, Baba H
  • Organizer: 9th AACR-Japanese Cancer Association Joint Conference (AACR-JCA)
  • Place of Presentation: Hyatt Regency Maui, Hawaii
  • Year and Date: 2013-02-23
• [Presentation] Association of IGF2 DMR0 hypomethylation in esophageal squamous cell carcinoma with poor prognosis (2013)
  • Author(s): Baba Y, Watanabe M, Murata A, Shigaki H, Iwagami S, Ishimoto T, Baba H
  • Organizer: 2013 ASCO Annual Meeting
  • Place of Presentation: Chicago, USA
• [Presentation] Association of IGF2 DMR0 hypomethylation in esophageal squamous cell carcinoma with poor prognosis. (2013)
  • Author(s): Yoshifumi Baba, Masayuki Watanabe, Asuka Murata, Hironobu Shigaki, Shiro Iwagami, Takatsugu Ishimoto, Hideo Baba
  • Organizer: ASCO 2013
  • Place of Presentation: Chicago(アメリカ)
• [Presentation] Hypomethylation of the IGF2 DMR0 in Esophageal Squamous Cell Carcinoma, Detected by Bisulfite Pyrosequencing, is Associated with Poor Prognosis (2013)
  • Author(s): 村田 飛鳥
  • Organizer: AACR-JCA
  • Place of Presentation: マウイ（アメリカ・ハワイ）
• [Presentation] 食道扁平上皮癌におけるIGF2 DMR0メチル化レベルと予後の関係 (2012)
  • Author(s): 村田 飛鳥
  • Organizer: 第23回日本消化器癌発生学会
  • Place of Presentation: ルネッサンスリゾートナルト（徳島県）