Functional analyses and developments of new therapies targeting LSD1 in gastrointestinal cancers

• Project/Area Number: 16K19941
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Digestive surgery
• Research Institution: Kumamoto University
• Principal Investigator: KOSUMI Keisuke 熊本大学, 医学部附属病院, 非常勤診療医師 (50594884)
• Research Collaborator: BABA Yoshifumi 熊本大学, 大学院生命科学研究部, 講師 (20599708) ; HARADA Kazuto 熊本大学, 医学部附属病院, 非常勤診療医師 (70608869) ; YAMAMURA Kensuke 熊本大学, 医学部附属病院, 非常勤診療医師 (10816507)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: がん代謝 / 消化器癌 / バイオマーカー / エピジェネティクス / がん免疫 / LSD1 / オートファジー / 腫瘍免疫 / 腸内細菌 / 予後予測マーカー / 炎症

Outline of Final Research Achievements

The aim of the current study is to investigate the significance of Lysine Specific Demethylase-1 (LSD1) using global human population-based database, and contribute to the development of the new treatments. No association was observed between tumor LSD1 expression, and PIK3CA mutation, NRF2, CD8+ T-cell density, FOXP3+ T-cell density, PD-L1, IDO1, or tumor-infiltrating lymphocytes (P > 0.14). However, we found the significant inverse association of LSD1 with LINE-1 methylation level and peritumoral lymphocytic reaction (P = 0.0019 and P = 0.017, respectively). Our findings support the possible influence of LSD1 on epigenetic change and anti-tumor immunity.

Research Products

• [Journal Article] Pyloroplasty may reduce weight loss 1 year after esophagectomy. (2018)
  • Author(s): Harada K, Yoshida N, Baba Y, Nakamura K, Kosumi K, Ishimoto T, Iwatsuki M, Miyamoto Y, Sakamoto Y, Ajani JA, Watanabe M, Baba H.
  • Journal Title: Dis Esophagus. Volume: Mar 1 Issue: 3
  • DOI: 10.1093/dote/dox127
  • Peer Reviewed
• [Journal Article] TIME (Tumor Immunity in the MicroEnvironment) classification based on tumor CD274 (PD-L1) expression status and tumor-infiltrating lymphocytes in colorectal carcinomas. (2018)
  • Author(s): Hamada T, Soong TR, Masugi Y, Kosumi K*, Nowak JA, da Silva A, Mu XJ, Twombly TS, Koh H, Yang J, Song M, Liu L, Gu M, Shi Y, Nosho K, Morikawa T, Inamura K, Shukla SA, Wu CJ, Garraway LA, Zhang X, Wu K, Meyerhardt JA, Chan AT, Glickman JN, Rodig SJ, Freeman GJ, Fuchs CS, Nishihara R, Giannakis M, Ogino S.
  • Journal Title: OncoImmunology. Volume: 21 Feb Issue: 7 Pages: e1442999-e1442999
  • DOI: 10.1080/2162402x.2018.1442999
  • Peer Reviewed
• [Journal Article] Minimally invasive esophagectomy may contribute to long-term respiratory function after esophagectomy for esophageal cancer. (2018)
  • Author(s): Kosumi K, Yoshida N, Okadome K, Eto T, Kuroda D, Ohuchi M, Kiyozumi Y, Nakamura K, Izumi D, Tokunaga R, Harada K, Mima K, Sawayama H, Ishimoto T, Iwatsuki M, Baba Y, Miyamoto Y, Watanabe M, Baba H.
  • Journal Title: Dis Esophagus. Volume: Feb 9. Issue: 6
  • DOI: 10.1093/dote/dox153
  • Peer Reviewed
• [Journal Article] The Prognostic Impact of Controlling Nutritional Status (CONUT) in Intrahepatic Cholangiocarcinoma Following Curative Hepatectomy: A Retrospective Single Institution Study. (2018)
  • Author(s): Miyata T, Yamashita YI, Higashi T, Taki K, Izumi D, Kosumi K, Tokunaga R, Nakagawa S, Okabe H, Imai K, Hashimoto D, Chikamoto A, Baba H.
  • Journal Title: World J Surg. Volume: 42(4) Issue: 4 Pages: 1085-1091
  • DOI: 10.1007/s00268-017-4214-1
  • Peer Reviewed
• [Journal Article] Aspirin exerts high anti-cancer activity in PIK3CA-mutant colon cancer cells. (2017)
  • Author(s): Gu M, Nishihara R, Chen Y, Li W, Shi Y, Masugi Y, Hamada T, Kosumi K, Liu L, da Silva A, Nowak JA, Twombly T, Du C, Koh H, Li W, Meyerhardt JA, Wolpin BM, Giannakis M, Aguirre AJ, Bass AJ, Drew DA, Chan AT, Fuchs CS, Qian ZR, Ogino S.
  • Journal Title: Oncotarget. Volume: 8(50) Issue: 50 Pages: 87379-87389
  • DOI: 10.18632/oncotarget.20972
  • Peer Reviewed
• [Journal Article] Tumor PDCD1LG2 (PD-L2) Expression and the Lymphocytic Reaction to Colorectal Cancer. (2017)
  • Author(s): Masugi Y, Nishihara R, Hamada T, Song M, da Silva A, Kosumi K, Gu M, Shi Y, Li W, Liu L, Nevo D, Inamura K, Cao Y, Liao X, Nosho K, Chan AT, Giannakis M, Bass AJ, Hodi FS, Freeman GJ, Rodig SJ, Fuchs CS, Qian ZR, Nowak JA, Ogino S.
  • Journal Title: Cancer Immunol Res. Volume: 5(11) Pages: 1046-1055
  • Peer Reviewed
• [Journal Article] Cell Cycle Protein Expression in Neuroendocrine Tumors: Association of CDK4/CDK6, CCND1, and Phosphorylated Retinoblastoma Protein With Proliferative Index. (2017)
  • Author(s): Shi Y, Qian ZR, Zhang S, Li W, Masugi Y, Li T, Chan JA, Yang J, Da Silva A, Gu M, Liu L, Hamada T, Kosumi K, Dutton T, Brais LK, Nishihara R, Fuchs CS, Ogino S, Kulke MH.
  • Journal Title: Pancreas. Volume: 46(10) Issue: 10 Pages: 1347-1353
  • DOI: 10.1097/mpa.0000000000000944
  • Peer Reviewed
• [Journal Article] Monitoring sputum culture in resected esophageal cancer patients with preoperative treatment. (2017)
  • Author(s): Kosumi K, Baba Y, Yamashita K, Ishimoto T, Nakamura K, Ohuchi M, Kiyozumi Y, Izumi D1, Tokunaga R, Harada K, Shigaki H, Kurashige J, Iwatsuki M, Sakamoto Y, Yoshida N, Watanabe M, Baba H
  • Journal Title: Dis Esophagus Volume: 30(12) Issue: 12 Pages: 1-9
  • DOI: 10.1093/dote/dox092
  • Peer Reviewed
• [Journal Article] Association Between Inflammatory Diet Pattern and Risk of Colorectal Carcinoma Subtypes Classified by Immune Responses to Tumor. (2017)
  • Author(s): Liu L, Nishihara R, Qian ZR, Tabung FK, Nevo D, Zhang X, Song M, Cao Y, Mima K, Masugi Y, Shi Y, da Silva A, Twombly T, Gu M, Li W, Hamada T, Kosumi K, Inamura K, Nowak JA, Drew DA, Lochhead P, Nosho K, Wu K, Wang M, Garrett WS, Chan AT, Fuchs CS, Giovannucci EL, Ogino S.
  • Journal Title: Gastroenterology. Volume: 153(6) Issue: 6 Pages: 1517-1530.e14
  • DOI: 10.1053/j.gastro.2017.08.045
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Body mass index and risk of colorectal carcinoma subtypes classified by tumor differentiation status. (2017)
  • Author(s): Hanyuda A, Cao Y, Hamada T, Nowak JA, Qian ZR, Masugi Y, da Silva A, Liu L, Kosumi K, Soong TR, Jhun I, Wu K, Zhang X, Song M, Meyerhardt JA, Chan AT, Fuchs CS, Giovannucci EL, Ogino S, Nishihara R.
  • Journal Title: Eur J Epidemiol. Volume: 32(5) Issue: 5 Pages: 393-407
  • DOI: 10.1007/s10654-017-0254-y
  • Peer Reviewed
• [Journal Article] Comparison of systemic inflammatory and nutritional scores in colorectal cancer patients who underwent potentially curative resection. (2017)
  • Author(s): Tokunaga R, Sakamoto Y, Nakagawa S, Izumi D, Kosumi K, Taki K, Higashi T, Miyata T, Miyamoto Y, Yoshida N, Baba H.
  • Journal Title: Int J Clin Oncol Volume: in press Issue: 4 Pages: 740-748
  • DOI: 10.1007/s10147-017-1102-5
  • Peer Reviewed
• [Journal Article] Preoperative controlling nutritional status (CONUT) is useful to estimate the prognosis after esophagectomy for esophageal cancer. (2017)
  • Author(s): Yoshida N, Harada K, Baba Y, Kosumi K, Iwatsuki M, Kinoshita K, Nakamura K, Sakamoto Y, Miyamoto Y, Karashima R, Mima K, Sawayama H, Ohuchi M, Chikamoto A, Imamura Y, Watanabe M, Baba H
  • Journal Title: Langenbeck Archiv Surg Volume: 402(2) Issue: 2 Pages: 333-41
  • DOI: 10.1007/s00423-017-1553-1
  • Peer Reviewed
• [Journal Article] LINE-1 methylation level and patient prognosis in pancreas cancer: pyrosequencing technology and literature review. (2017)
  • Author(s): Yamamura K, Kosumi K, Baba Y, Harada K, Zhang X, Zhou L, Kitano Y, Arima K, Kaida T, Takeyama H, Higashi T, Imai K, Hashimoto D, Chikamoto A, Tan X, Baba H.
  • Journal Title: Surg Today Volume: in press
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Aspirin Use and Colorectal Cancer Survival According to Tumor CD274 (Programmed Cell Death 1 Ligand 1) Expression Status. (2017)
  • Author(s): Hamada T, Cao Y, Qian ZR, Masugi Y, Nowak JA, Yang J, Song M, Mima K, Kosumi K, Liu L, Shi Y, da Silva A, Gu M, Li W, Keum N, Zhang X, Wu K, Meyerhardt JA, Giovannucci EL, Giannakis M, Rodig SJ, Freeman GJ, Nevo D, Wang M, Chan AT, Fuchs CS, Nishihara R, Ogino S.
  • Journal Title: J Clin Oncol Volume: - Issue: 16 Pages: 1836-1844
  • DOI: 10.1200/jco.2016.70.7547
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Tumor SQSTM1 (p62) expression and T cells in colorectal cancer. (2017)
  • Author(s): Kosumi K, Masugi Y, Yang J, Qian ZR, Kim SA, Li W, Shi Y, da Silva A, Hamada T, Liu L, Gu M, Twombly TS, Cao Y, Barbie DA, Nosho K, Baba H, Garrett WS, Meyerhardt JA, Giovannucci EL, Chan AT, Fuchs CS, Ogino S, Nishihara R.
  • Journal Title: Oncoimmunology Volume: 6(3) Issue: 3 Pages: e1284720-e1284720
  • DOI: 10.1080/2162402x.2017.1284720
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Dietary glycemic and insulin scores and colorectal cancer survival by tumor molecular biomarkers. (2017)
  • Author(s): Keum N, Yuan C, Nishihara R, Zoltick E, Hamada T, Martinez Fernandez A, Zhang X, Hanyuda A, Liu L, Kosumi K, Nowak JA, Jhun I, Soong TR, Morikawa T, Tabung FK, Qian ZR, Fuchs CS, Meyerhardt JA, Chan AT, Ng K, Ogino S, Giovannucci EL, Wu K.
  • Journal Title: Int J Cancer Volume: 140(12) Issue: 12 Pages: 2648-2656
  • DOI: 10.1002/ijc.30683
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Association of Dietary Patterns With Risk of Colorectal Cancer Subtypes Classified by Fusobacterium Nucleatum in Tumor Tissue. (2017)
  • Author(s): Mehta RS, Nishihara R, Cao Y, Song M, Mima K, Qian ZR, Nowak JA, Kosumi K, Hamada T, Masugi Y, Bullman S, Drew DA, Kostic AD, Fung TT, Garrett WS, Huttenhower C, Wu K, Meyerhardt JA, Zhang X, Willett WC, Giovannucci EL, Fuchs CS, Chan AT, Ogino S.
  • Journal Title: JAMA Oncol. Volume: - Issue: 7 Pages: 921-921
  • DOI: 10.1001/jamaoncol.2016.6374
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Fusobacterium nucleatum in Colorectal Carcinoma Tissue According to Tumor Location. (2016)
  • Author(s): Mima K, Cao Y, Chan AT, Qian ZR, Nowak JA, Masugi Y, Shi Y, Song M, da Silva A, Gu M, Li W, Hamada T, Kosumi K, Hanyuda A, Liu L, Kostic AD, Giannakis M, Bullman S, Brennan CA, Milner DA, Baba H, Garraway LA, Meyerhardt JA, Garrett WS, Huttenhower C, Meyerson M, Giovannucci EL, Fuchs CS, Nishihara R, Ogino S.
  • Journal Title: Clin Transl Gastroenterol Volume: 7(11) Issue: 11 Pages: e200-e200
  • DOI: 10.1038/ctg.2016.53
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] UHRF1 regulates global DNA hypomethylation and is associated with poor prognosis in esophageal squamous cell carcinoma (2016)
  • Author(s): K. Nakamura, Y. Baba, K. Kosumi, K. Harada, H. Shigaki, K. Miyake, Y. Kiyozumi, M. Ohuchi, J. Kurashige, T. Ishimoto, M. Iwatsuki, Y. Sakamoto, N. Yoshida, M. Watanabe, M. Nakao, and H. Baba.
  • Journal Title: Oncotarget Volume: 7 Issue: 36 Pages: 57821-57831
  • DOI: 10.18632/oncotarget.11067
  • Peer Reviewed / Open Access
• [Journal Article] Prognostic and clinical impact of PIK3CA mutation in gastric cancer: pyrosequencing technology and literature review. (2016)
  • Author(s): Harada K, Baba Y, Shigaki H, Ishimoto T, Miyake K, Kosumi K, Tokunaga R, Izumi D, Ohuchi M, Nakamura K, Kiyozumi Y, Kurashige J, Iwatsuki M, Miyamoto Y, Sakamoto Y, Yoshida N, Watanabe M, Baba H.
  • Journal Title: BMC Cancer. Volume: 16 Issue: 1 Pages: 400-400
  • DOI: 10.1186/s12885-016-2422-y
  • Peer Reviewed / Open Access
• [Journal Article] KRAS, BRAF, PIK3CA Mutations and Patient Prognosis in 126 Pancreatic Cancers: Pyrosequencing Technology and Literature Review. (2016)
  • Author(s): Zhou L, Baba Y, Kitano Y, Miyake K, Zhang X, Yamamura K, Kosumi K, Kaida T, Arima K, Taki K, Higashi T, Imai K, Hashimoto D, Yamashita Y, Chikamoto A, Beppu T, Tan X, Baba H.
  • Journal Title: Med Oncol Volume: 33(4) Issue: 4 Pages: 32-32
  • DOI: 10.1007/s12032-016-0745-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Bifidobacterium Genus in Colorectal Carcinoma Tissue in relation to Tumor Characteristics and Patient Survival. (2018)
  • Author(s): Borowsky J, Kosumi K*, Hamada T, Koh H, Bullman S, Twombly TS, Masugi Y, Liu L, da Silva A, Chen Y, Du C, Gu M, Li C, Li W, Liu H, Shi Y, Song M, Nosho K, Nowak JA, Nishihara R, Baba H, Zhang X, Wu K, Huttenhower C, Garrett WS, Meyerson M, Lennerz JK, Giannakis M, Chan AT, Meyerhardt JA, Fuchs CS, Ogino S.
  • Organizer: 1.ASIP Annual Meeting at Experimental Biology 2018
• [Presentation] Bifidobacterium genus in colorectal carcinoma tissue in relation to tumor characteristics and patient survival. (2018)
  • Author(s): Kosumi K, Hamada T, Koh H, Borowsky J, Bullman S, Twombly TS, Masugi Y, Liu L, da Silva A, Chen Y, Du C, Gu M, Li C, Li W, Liu H, Shi Y, Song M, Nosho K, Nowak JA, Nishihara R, Baba H, Zhang X, Wu K, Huttenhower C, Garrett WS, Meyerson M, Lennerz JK, Giannakis M, Chan AT, Meyerhardt JA, Fuchs CS, Ogino S
  • Organizer: The 4th International Molecular Pathological Epidemiology (MPE) Meeting.