Basic research for early diagnosis of lung carcinomas by the application of DNA methylation analysis

• Project/Area Number: 24701008
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor diagnosis
• Research Institution: Kagoshima University
• Principal Investigator: YOKOYAMA Seiya 鹿児島大学, 医歯(薬)学総合研究科, 助教 (20569941)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: lung adenocarcinomas / mucin / DNA methylation / demethylation / ten eleven translocation / 肺癌 / ムチン / エピジェネティクス / DNA脱メチル化

Research Abstract

Lung cancer is still a disease of high mortality, despite advanced diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in lung neoplasms. We have developed a novel 'methylation-specific electrophoresis (MSE)' method to analyze the DNA methylation status of MUC1 and MUC4 by high sensitivity and resolution.
By using the MSE method, we evaluated lung tissue samples from 33 patients with various lung lesions. Our results showed that the TET1 was important factor for DNA demethylation to regulate the expression of MUC1 and MUC4 in lung cancer. The analysis of the epigenetic changes of MUC1 and MUC4 may be useful for diagnosing the carcinogenic risk and predicting outcome of patients.

Research Products

• [Journal Article] Diagnosis of pancreatic neoplasms using a novel method of DNA methylation analysis of mucin expression in pancreatic juice (2014)
  • Author(s): Yokoyama S, Kitamoto S, Higashi M, Goto Y, Hara T, Ikebe D, Yamaguchi T, Arisaka Y, Niihara, Nishimata H, Tanaka S, Takaori K, Batra S K, Yonezawa S
  • Journal Title: PLoS ONE Volume: 9(4) Issue: 4 Pages: e93760-e93760
  • DOI: 10.1371/journal.pone.0093760
  • Peer Reviewed / Open Access
• [Journal Article] Pathobiological implications of mucin (MUC) expression in the outcome of small bowel cancer (2014)
  • Author(s): Shibahara H, Higashi M, Koriyama C, Yokoyama S, Kitazono I, Yasuhiro K, Narita M, Kuze S, Takanori K, Mita S, Arai T, Kato T, Yuasa N, Yamaguchi R, Kubota H, Suzuki H, Baba S, Rousseau K, Batra S K, Yonezawa S
  • Journal Title: PLoS ONE Volume: 9(4) Issue: 4 Pages: e86111-e86111
  • DOI: 10.1371/journal.pone.0086111
  • Peer Reviewed / Open Access
• [Journal Article] Expression of MUC4 mucin is observed mainly in the intestinal-type of intraductal papillary mucinous neoplasm of the pancreas (2013)
  • Author(s): Kitazono I, Higashi M, Kitamoto S, Yokoyama S, Horinouchi M, Osako M, Shimizu T, Tabata M, Batra S K, Goto M, Yonezawa S
  • Journal Title: Pancreas Volume: 42(7) Issue: 7 Pages: 1120-1128
  • DOI: 10.1097/mpa.0b013e3182965915
  • Peer Reviewed
• [Journal Article] MUC1 enhances hypoxia-driven angiogenesis through the regulation of multiple proangiogenic factors (2013)
  • Author(s): Sho Kitamoto, Soiya Yokoyama, Michiyo Higashi, Norishlge Yamada, Sonshin Takao, Suguru Yonezawa
  • Journal Title: Oncogene Volume: 32(39) Issue: 39 Pages: 4614-4621
  • DOI: 10.1038/onc.2012.478
  • Peer Reviewed
• [Journal Article] Identification of mucins by using a method involving a combination of on-membrane chemical deglycosylation and immunostaining (2013)
  • Author(s): Matsuno YK, Dong W, Yokoyama S, Yonezawa S, Narimatsu H, Kameyama A
  • Journal Title: J Immunol Methods Volume: 394 Issue: 1-2 Pages: 125-130
  • DOI: 10.1016/j.jim.2013.06.002
  • Peer Reviewed
• [Journal Article] 特集 : 粘液産生性胆道系腫瘍の再出発-エビデンスとしての画像と病理「胆道系腫瘍における粘液産生の組織学的側面」 (2013)
  • Author(s): 東美智代、柴原弘明、後藤優子、平木翼、横山勢也、米澤傑
  • Journal Title: 胆と膵 Volume: 34(5) Pages: 353-358
• [Journal Article] 特集胆膵病理II : 胆膵共通のトピックス【胆膵共通疾患とトピックス】膵胆道腫瘍におけるMUC発現 (2013)
  • Author(s): 米澤傑、東美智代、横山勢也、後藤優子、北島信一
  • Journal Title: 病理と臨床 Volume: 31(4) Pages: 399-408
• [Journal Article] MUC4 and MUC1 Expression in Adenocarcinoma of the Stomach Correlates with Vessel Invasion and Lymph Node Metastasis : An Immunohisto chemical Study of Early Gastric Cancer. (2013)
  • Author(s): Yukihiro Tamura, Michiyo Higashi, Sho Kitamoto, Seiya Yokoyama, Masahiko Osako, Michiko Horinouchi, Takeshi Shimizu, Mineo Tabata, Surinder K. Batra, Masamichi Goto, Suguru Yonezawa
  • Journal Title: PLoS ONE Volume: (in press) Issue: 11 Pages: e49251-e49251
  • DOI: 10.1371/journal.pone.0049251
  • Peer Reviewed
• [Journal Article] 特集 胆膵病理II:胆膵共通のトピックス【胆膵共通疾患とトピックス】膵胆道腫瘍におけるMUC発現． (2013)
  • Author(s): 米澤 傑、東美智代、横山勢也、後藤優子、北島信一
  • Journal Title: 病理と臨床 Volume: 31(4) Pages: 399-408
• [Journal Article] 特集：粘液産生性胆道系腫瘍の再出発－エビデンスとしての画像と病理 「胆道系腫瘍における粘液産生の組織学的側面」. (2013)
  • Author(s): 東美智代、柴原弘明、後藤優子、平木 翼、横山勢也、米澤 傑
  • Journal Title: 胆と膵 Volume: 34(5) Pages: 353-358
  • Peer Reviewed
• [Journal Article] Expression of MUC17 Is Regulated by HIF1α-mediated Hypoxic Responses and Requires a Methylation-free Hypoxia Responsible Element in Pancreatic Cancer. (2012)
  • Author(s): Sho Kitamoto, Seiya Yokoyama, Michiyo Higashi, Norishige Yamada, Shyuichiro Matsubara, Sonshin Takao, Surinder K. Batra, Suguru Yonezawa
  • Journal Title: PLoS ONE Volume: 7(9) Issue: 9 Pages: e44108-e44108
  • DOI: 10.1371/journal.pone.0044108
  • Peer Reviewed
• [Journal Article] A novel anti-MUC1 antibody against the MUC1 cytoplasmic tail domain : use in sensitive identification of poorly differentiated cells in adenocarcinoma of the stomach (2012)
  • Author(s): Suguru Yonezawa
  • Journal Title: Gastric Cancer Volume: (In press) Issue: 4 Pages: 370-381
  • DOI: 10.1007/s10120-011-0125-2
  • Peer Reviewed
• [Journal Article] The application of Methylation specific electrophoresis (MSE) to DNA methylation analysis of the 5' CpG island of mucin in cancer cells (2012)
  • Author(s): Seiya Yokoyama
  • Journal Title: BMC Cancer Volume: 12(In press) Issue: 1 Pages: 67-67
  • DOI: 10.1186/1471-2407-12-67
  • Peer Reviewed
• [Journal Article] Pathobiological implications of expression of MUC16/CA125 in intrahepatic cholangiocarcinoma-mass formina type (2012)
  • Author(s): Michiyo Higashi
  • Journal Title: Pathobiology Volume: 79 Issue: 2 Pages: 101-106
  • DOI: 10.1159/000335164
  • Peer Reviewed
• [Journal Article] 胆管内乳頭状腫瘍(IPNB) : 粘液,MUC発現からのアプローチ (2012)
  • Author(s): 東美智代、横山勢也、北本祥、米澤傑
  • Journal Title: 肝胆膵 Volume: 65(3) Pages: 487-494
• [Journal Article] 癌におけるムチンの臨床病理学的意義および診断への応用-難治性膵胆管癌の早期診断に向けて- (2012)
  • Author(s): 米澤傑、東美智代、横山勢也、北本祥、山田宗茂
  • Journal Title: MEDICAL TECNOLOGY Volume: 40(4) Pages: 419-425
• [Presentation] TET1 was important factor for DNA demethylation to regulate the expression of MUC1 and MUC4 in lung cancer. (2014)
  • Author(s): Seiya Yokoyama, Sho Kitamoto, Hideaki Tsutsumida, Joji Wakimoto, Michiyo Higashi, Suguru Yonezawa
  • Organizer: 23rd Biennial EACR Congress
  • Place of Presentation: International Congress Centre Munich (München, Germany)
• [Presentation] Application of a novel DNA methylation analysis method (MSE) for mucin expression in pancreatic, biliary and pulmonary neoplasms (2013)
  • Author(s): Yonezawa S, Yokoyama S, Kitamoto S, Higashi M
  • Organizer: MUCINS IN HEALTH AND DISEASE (12th International Workshop on Carcinoma-associated Mucins)
  • Place of Presentation: Robinson College (Cambridge, UK)
• [Presentation] Diagnosis of pancreatic neoplasms by application of a novel DNA methylation analysis method (MSE) for mucin expression in pancreatic juices (2013)
  • Author(s): Yonezawa S, Yokoyama S, Higashi M, Goto Y, Kitajima S
  • Organizer: Worldwide Innovative Networking in personalized cancer medicine
  • Place of Presentation: Le Palais des Congres (Paris, France)
• [Presentation] Examination of mucin expression including a novel DNA methylation analysis method (MSE) : Its application for diagnosis of human pancreatic neoplasms (2013)
  • Author(s): Yonezawa S, Yokoyama S, Goto Y, Higashi M
  • Organizer: 19th International Charles Heidelberger Symposium on Cancer Research
  • Place of Presentation: William Willis Hall (Kagoshima, Japan)
• [Presentation] DNA promoter methylation status and mRNA expression of MUC1 in human lung cancer (2013)
  • Author(s): Yokoyama S, Kitamoto S, Tsutsumida H, Wakimoto J, Higashi M, Yonezawa S
  • Organizer: 19th International Charles Heidelberger Symposium on Cancer Research
  • Place of Presentation: William Willis Hall (Kagoshima, Japan)
• [Presentation] 浸潤性膵癌におけるEUS-FNABでのムチン発現 (2013)
  • Author(s): 東 美智代、 横山勢也、後藤優子、平木 翼、後藤正道、米澤 傑
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: ロイトン札幌 （札幌市）
• [Presentation] 膵癌におけるMUC1遺伝子のメチル化ステータスとmRNA発現解析 (2013)
  • Author(s): 横山勢也、 北本 祥、堤田英明、脇本譲二、東美智代、米澤 傑
  • Organizer: 第102回日本病理学会総会
  • Place of Presentation: ロイトン札幌 （札幌市）
• [Presentation] Application of a novel DNA methylation analysis method (MSE) for mucin expression in pancreatic, biliary and pulmonary neoplasms (2013)
  • Author(s): Suguru Yonezawa, Seiya Yokoyama, Sho Kitamoto, Michiyo Higashi
  • Organizer: MUCINS IN HEALTH AND DISEASE (12th International Workshop on Carcinoma-associated Mucins)
  • Place of Presentation: King's College (London, UK)
• [Presentation] Diagnosis of pancreatic neoplasms by application of a novel DNA methylation analysis method (MSE) for mucin expression in pancreatic juices (2013)
  • Author(s): Yonezawa Suguru, Yokoyama Seiya, Higashi Michiyo, Goto Yuko, Kitajima Shinichi
  • Organizer: Worldwide Innovative Networking in personalized cancer medicine
  • Place of Presentation: "Le Palais des Congres (Paris, FRANCE)
• [Presentation] DNA promoter methylation status and mRNA expression status of MUC1 in lung cancer (2013)
  • Author(s): 横山勢也、 北本祥、堤田英明、東美智代、米澤傑
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜 神奈川県横浜市
• [Presentation] Diagnosis of pancreatic neoplasms by a novel high sensitive DNA methylation analysis method “MSE”for pancreatic juices (2013)
  • Author(s): 米澤傑、 横山勢也、東美智代
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜 神奈川県横浜市
• [Presentation] DNA promoter methylation status and mRNA expression of MUC1 in human lung cancer (2013)
  • Author(s): Seiya Yokoyama, Sho Kitamoto, Hideyuki Tsutsumida, Jyouji Wakimoto, Michiyo Higashi, Suguru Yonezawa
  • Organizer: 19th International Charles Heidelberger Symposium on Cancer Research
  • Place of Presentation: 鹿児島市
• [Presentation] 肺癌におけるMUC1遺伝子のメチル化ステータスとmRNA発現解析 (2013)
  • Author(s): 横山勢也、北本祥、堤田英明、脇本譲二、東美智代、米澤傑
  • Organizer: 第102回日本病理学会学術総会
  • Place of Presentation: 札幌市
• [Presentation] TET1 was important factor for DNA demethylation to regulate the expression of MUC1 and MUC4 in lung cancer (2012)
  • Author(s): Yokoyama S, Kitamoto S, Tsutsumida H, Wakimoto J, Higashi M, Yonezawa S
  • Organizer: 23^<rd> Biennial Ccongress of the European Association for Cancer Research
  • Place of Presentation: International Congress Center Munich (Munchen, Germany) (発表確定)
• [Presentation] MUC1 Enhances Hypoxia-Driven Angiogenesis Through the Regulation of Multiple Proangiogenic Factors (2012)
  • Author(s): Kitamoto S, Yokoyama S, Higashi M, Yamada N, Takao S, Yonezawa S
  • Place of Presentation: 京都国際コンベンションセンター(京都)
• [Presentation] The Application of New DNA Methylation Analysis, Designated Methylation Specific Electrophoresis (MSE) for Pancreatic Juice Analysis (2012)
  • Author(s): Yokoyama S, kitamoto S, Hara T, Arisaka Y, Takaori K, Yamamoto T, Niihara T, Nishimata H, Tanaka S, Higashi M, Yonezawa S
  • Place of Presentation: 京都国際コンベンションセンター(京都)
• [Presentation] CTGF is enhanced by hypoxia through nuclear recruitment of MUC1 in pancreatic cancer (2012)
  • Author(s): Kitamoto S, Higashi M, Yokoyama S, Takao S, Yonezawa S
  • Organizer: 22nd Biennial Congress of the European Association for Cancer Research
  • Place of Presentation: バルセロナ国際会議場(Barcelona, Spain)
• [Presentation] 新規高感度DNAメチル化解析法（MSE法）による膵IPMN亜型の早期診断へ向けた応用 (2012)
  • Author(s): 横山勢也、北本祥、北条いづみ、東美智代、米澤傑
  • Organizer: 第101回日本病理学会学術総会
  • Place of Presentation: 東京都
• [Presentation] DNA promoter methylation status and mRNA expression of MUC1 in human bile duct cancer (2012)
  • Author(s): Seiya Yokoyama, Sho Kitamoto, Michiyo Higashi, Suguru Yonezawa
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市
• [Presentation] 新しい高感度DNAメチル化高感度検出法(MSE法)を用いた膵液中のムチン発現遺伝子解析による膵腫瘍の診断
  • Author(s): 米澤 傑、 東美智代、横山勢也、後藤優子、平木 翼、北島信一、原 太郎、有坂好史、新原 亨、高折恭一
  • Organizer: 第30回日本胆膵病態・生理研究会
  • Place of Presentation: ウエスティンホテル仙台 （仙台市）
• [Remarks] 鹿児島大学医歯学総合絵研究科先進治療科学専攻腫瘍学講座人体がん病理学
  • URL: http://www.kufm.kagoshima-u.ac.jp/~byouri2/
• [Remarks] 腫瘍学講座 人体がん病理学 (旧第二病理)
  • URL: http://www.kufm.kagoshima-u.ac.jp/~byouri2/
• [Remarks] 鹿児島大学院 人体がん病理学
  • URL: http://www.kufm.kagoshima-u.ac.jp/~byouri2/
• [Patent(Industrial Property Rights)] METHOD FOR DIAGNOSING TYPE OF PANCREATIC TUMOR (2012)
  • Inventor(s): 横山勢也、米澤 傑、北本 祥
  • Industrial Property Rights Holder: 鹿児島大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-06-29
  • Overseas
• [Patent(Industrial Property Rights)] NOVEL DNA METHYLATION ANALYSIS METHOD (2011)
  • Inventor(s): 横山勢也、米澤 傑
  • Industrial Property Rights Holder: 鹿児島大学
  • Industrial Property Rights Type: 特許
  • Filing Date: 2011-04-21
  • Overseas