Genomic Profile of Responders to Preoperative Chemoradiotherapy for Advanced Rectal Cancer

• Project/Area Number: 15K10156
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: Akiyoshi Takashi 公益財団法人がん研究会, 有明病院 消化器外科, 医長 (50625598)
• Co-Investigator(Kenkyū-buntansha): 森 誠一 公益財団法人がん研究会, がんプレシジョン医療研究センター 次世代がん研究シーズ育成プロジェクト, プロジェクトリーダー (10334814)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 直腸がん / 術前放射線化学療法 / 全エクソンシークエンス / 直腸癌

Outline of Final Research Achievements

We performed whole-exome sequencing (n=74) using pre-treatment biopsies from patients with advanced rectal cancer treated with preoperative chemoradiotherapy (CRT). We identified five hypermutated tumors, all of which were responders. A comparative analysis among the non-hypermutated tumors (n=69) showed a significantly higher number of non-silent mutation and higher CD8+ T-cell infiltration in responders than in non-responders. Our finding suggests that mutation burden and resultant neoantigen burden before CRT might be a critical determinant of patient responses to CRT.

Research Products

• [Journal Article] Pattern of programmed cell death-ligand 1 expression and CD8-positive T-cell infiltration before and after chemoradiotherapy in rectal cancer (2018)
  • Author(s): Ogura Atsushi、Akiyoshi Takashi、Yamamoto Noriko、Kawachi Hiroshi、Ishikawa Yuichi、Mori Seiichi、Oba Koji、Nagino Masato、Fukunaga Yosuke、Ueno Masashi
  • Journal Title: European Journal of Cancer Volume: 91 Pages: 11-20
  • DOI: 10.1016/j.ejca.2017.12.005
  • Peer Reviewed / Open Access
• [Journal Article] Skeletal muscle loss is an independent negative prognostic factor in patients with advanced lower rectal cancer treated with neoadjuvant chemoradiotherapy (2018)
  • Author(s): Takeda Y, Akiyoshi T, Matsueda K, Fukuoka H, Ogura A, Miki H, Hiyoshi Y, Nagasaki T, Konishi T, Fujimoto Y, Fukunaga Y, Ueno M
  • Journal Title: PLos One Volume: 13 Issue: 4 Pages: e0195406-e0195406
  • DOI: 10.1371/journal.pone.0195406
  • Peer Reviewed / Open Access
• [Journal Article] Change in clinical outcomes during the transition of adjuvant chemotherapy for stage III colorectal cancer (2017)
  • Author(s): Osumi Hiroki、Shinozaki Eiji、Suenaga Mitsukuni、Wakatsuki Takeru、Nakayama Izuma、Matsushima Tomohiro、Ogura Mariko、Ichimura Takashi、Takahari Daisuke、Chin Keisho、Nagasaki Toshiya、Konishi Tsuyoshi、Akiyoshi Takashi、Fujimoto Yoshiya、Nagayama Satoshi、Fukunaga Yosuke、Ueno Masashi、Yamaguchi Kensei
  • Journal Title: PLos One Volume: 12 Issue: 5 Pages: e0176745-e0176745
  • DOI: 10.1371/journal.pone.0176745
  • Peer Reviewed / Open Access
• [Journal Article] Pretreatment Serum Carbohydrate Antigen 19-9 Concentration Is a Predictor of Survival of Patients Who Have Undergone Curative Resection of Stage IV Rectal Cancer (2017)
  • Author(s): Miki Hisanori、Akiyoshi Takashi、Ogura Atsushi、Nagasaki Toshiya、Konishi Tsuyoshi、Fujimoto Yoshiya、Nagayama Satoshi、Noma Hisashi、Saiura Akio、Fukunaga Yosuke、Ueno Masashi
  • Journal Title: Dig Surg Volume: 印刷中 Issue: 5 Pages: 389-396
  • DOI: 10.1159/000480247
  • Peer Reviewed
• [Journal Article] Serum miR-143 levels predict the pathological response to neoadjuvant chemoradiotherapy in patients with locally advanced rectal cancer (2017)
  • Author(s): Hiyoshi Y, Akiyoshi T, Inoue R, Murofushi K, Yamamoto N, Fukunaga Y, Ueno M, Baba H, Mori S, Yamaguchi T
  • Journal Title: Oncotarget Volume: 印刷中 Issue: 45 Pages: 79201-79211
  • DOI: 10.18632/oncotarget.16760
  • Peer Reviewed / Open Access
• [Journal Article] Development and validation of a prognostic nomogram for colorectal cancer after radical resection based on individual patient data from three large-scale phase III trials (2017)
  • Author(s): Honda Michitaka、Oba Koji、Akiyoshi Takashi、Maeda Hiromichi、Kashiwabara Kosuke、Kanda Mitsuro、Mayanagi Shuhei、Aoyama Toru、Hamada Chikuma、Sadahiro Sotaro、Fukunaga Yosuke、Ueno Masashi、Sakamoto Junichi、Saji Shigetoyo、Yoshikawa Takaki
  • Journal Title: Oncotarget Volume: 8 Issue: 58 Pages: 99150-99160
  • DOI: 10.18632/oncotarget.21845
  • Peer Reviewed / Open Access
• [Journal Article] Clinicopathological characteristics of young patients with sporadic colorectal cancer. (2016)
  • Author(s): Murata A, Akiyoshi T et al
  • Journal Title: Surgery Today Volume: 46 Issue: 10 Pages: 1166-1175
  • DOI: 10.1007/s00595-015-1298-9
  • Peer Reviewed
• [Journal Article] RAS mutation is a prognostic biomarker in colorectal cancer patients with metastasectomy. (2016)
  • Author(s): Osumi H, Shinozaki E, Suenaga M, Matsusaka S, Konishi T, Akiyoshi T, Fujimoto Y, Nagayama S, Fukunaga Y, Ueno M, Mise Y, Ishizawa T, Inoue Y, Takahashi Y, Saiura A, Uehara H, Mun M, Okumura S, Mizunuma N, Miki Y, Yamaguchi T.
  • Journal Title: Int J Cancer Volume: Epub ahead of print Issue: 4 Pages: 803-811
  • DOI: 10.1002/ijc.30106
  • Peer Reviewed
• [Journal Article] Indications for Lateral Pelvic Lymph Node Dissection Based on Magnetic Resonance Imaging Before and After Preoperative Chemoradiotherapy in Patients with Advanced Low-Rectal Cancer. (2015)
  • Author(s): Akiyoshi T et al.
  • Journal Title: Ann Surg Oncol Volume: Suppl 3 Issue: S3 Pages: 614-620
  • DOI: 10.1245/s10434-015-4565-5
  • Peer Reviewed
• [Journal Article] Prognostic Impact of Neutrophil-to-Lymphocyte Ratio in Patients with Advanced Low Rectal Cancer Treated with Preoperative Chemoradiotherapy (2015)
  • Author(s): Nagasaki T, Akiyoshi T, et al.
  • Journal Title: Dig Surg Volume: 32 Issue: 6 Pages: 496-503
  • DOI: 10.1159/000441396
  • Peer Reviewed
• [Presentation] Low expression of miR-143 in serum as a predictive marker for good pathological response to neoadjuvant chemoradiotherapy in locally advanced rectal cancer patients (2016)
  • Author(s): Hiyoshi Y, Akiyoshi T et al.
  • Organizer: European Society of Coloproctology 2016
  • Place of Presentation: Milan, Italy
  • Year and Date: 2016-09-20
  • Int'l Joint Research