Clinical burden of PD-L1-PD-1 axis in colorectal cancer

• Project/Area Number: 16K10533
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Mie University
• Principal Investigator: Hiro Junichiro 三重大学, 医学系研究科, 助教 (70444437)
• Co-Investigator(Kenkyū-buntansha): 問山 裕二 三重大学, 医学部附属病院, 准教授 (00422824) ; 井上 靖浩 三重大学, 医学系研究科, 客員准教授 (20324535) ; 楠 正人 三重大学, 医学系研究科, 教授 (50192026)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 大腸癌 / PD-１ / PD-L1 / 遺伝子解析 / マイクロサテライト不安定性 / 腫瘍浸潤Ｔリンパ球 / バイオマーカー / 免疫療法

Outline of Final Research Achievements

The aim of this study was to clarify clinical burden of PD-1-PD-L1 axis in colorectal cancer patients. Interesting, elevated expression of PD-L1 was significantly correlated with poor overall survival and disease-free survival in CRC patients. Furthermore, assessment od CTLA4 concentration in preoperative serum could also identify high-risk population for recurrence and survival in CRC.

Academic Significance and Societal Importance of the Research Achievements

本研究結果を用いることで、あらたな予後予測マーカーとなりうるほか、免疫チェックポイント阻害剤の効果予測因子となる可能性が示唆された。

Research Products

• [Journal Article] Soluble PD-L1 Expression in Circulation as a Predictive Marker for Recurrence and Prognosis in Gastric Cancer: Direct Comparison of the Clinical Burden Between Tissue and Serum PD-L1 Expression. (2019)
  • Author(s): Shigemori T, Toiyama Y, Okugawa Y, Yamamoto A, Yin C, Narumi A, Ichikawa T, Ide S, Shimura T, Fujikawa H, Yasuda H, Hiro J, Yoshiyama S, Ohi M, Araki T, Kusunoki M.
  • Journal Title: Ann Surg Oncol. Volume: 26 Issue: 3 Pages: 876-883
  • DOI: 10.1245/s10434-018-07112-x
  • Peer Reviewed / Open Access
• [Journal Article] Clinical Impact of Muscle Quantity and Quality in Colorectal Cancer Patients: A Propensity Score Matching Analysis. (2018)
  • Author(s): Okugawa Y, Toiyama Y, Yamamoto A, Shigemori T, Yin C, Narumi A, Omura Y, Ide S, Kitajima T, Fujikawa H, Yasuda H, Hiro J, Yoshiyama S, Kobayashi M, Araki T, McMillan DC, Miki C, Kusunoki M.
  • Journal Title: JPEN J Parenter Enteral Nutr. Volume: 42(8) Issue: 8 Pages: 1322-1333
  • DOI: 10.1002/jpen.1171
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Feasibility of Assessing Prognostic Nutrition Index in Patients With Rectal Cancer Who Receive Preoperative Chemoradiotherapy (2018)
  • Author(s): Okugawa Y, Toiyama Y, Oki S, Ide S, Yamamoto A, Ichikawa T, Kitajima T, Fujikawa H, Yasuda H, Saigusa S, Hiro J, Yoshiyama S, Kobayashi M, Araki T, Kusunoki M
  • Journal Title: JPEN J Parenter Enteral Nutr. Volume: 42(6) Issue: 6 Pages: 998-1007
  • DOI: 10.1002/jpen.1041
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Enhanced AZIN1 RNA editing and overexpression of its regulatory enzyme ADAR1 are important prognostic biomarkers in gastric cancer (2018)
  • Author(s): Okugawa Yoshinaga、Toiyama Yuji、Shigeyasu Kunitoshi、Yamamoto Akira、Shigemori Tsunehiko、Yin Chengzeng、Ichikawa Takashi、Yasuda Hiromi、Fujikawa Hiroyuki、Yoshiyama Shigeyuki、Hiro Junichiro、Ohi Masaki、Araki Toshimitsu、Kusunoki Masato、Goel Ajay
  • Journal Title: Journal of Translational Medicine Volume: 16 Issue: 1 Pages: 366-366
  • DOI: 10.1186/s12967-018-1740-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Prognostic impact of sarcopenia and its correlation with circulating miR-21 in colorectal cancer patients. (2018)
  • Author(s): Okugawa Y, Yao L, Toiyama Y, Yamamoto A, Shigemori T, Yin C, Omura Y, Ide S, Kitajima T, Shimura T, Fujikawa H, Yasuda H, Hiro J, Yoshiyama S, Kobayashi M, Tanaka K, Inoue Y, Araki T, Miki C, Kusunoki M.
  • Journal Title: Oncol Rep. Volume: 39 Pages: 1555-1564
  • DOI: 10.3892/or.2018.6270
  • Peer Reviewed
• [Journal Article] Successful identification of a predictive biomarker for lymph node metastasis in colorectal cancer using a proteomic approach. (2017)
  • Author(s): Mori K, Toiyama Y, Otake K, Ide S, Imaoka H, Okigami M, Okugawa Y, Fujikawa H, Saigusa S, Hiro J, Kobayashi M, Ohi M, Tanaka K, Inoue Y, Kobayashi Y, Mohri Y, Kobayashi I, Goel A, Kusunoki M.
  • Journal Title: Oncotarget. Volume: 8 Issue: 63 Pages: 106935-106947
  • DOI: 10.18632/oncotarget.22149
  • Peer Reviewed / Open Access
• [Journal Article] Proteomics analysis of differential protein expression identifies heat shock protein 47 as a predictive marker for lymph node metastasis in patients with colorectal cancer. (2017)
  • Author(s): Mori K, Toiyama Y, Otake K, Fujikawa H, Saigusa S, Hiro J, Kobayashi M, Ohi M, Tanaka K, Inoue Y, Kobayashi Y, Kobayashi I, Mohri Y, Goel A, Kusunoki M.
  • Journal Title: Int J Cancer. Volume: 140 Issue: 6 Pages: 1425-1435
  • DOI: 10.1002/ijc.30557
  • Peer Reviewed
• [Journal Article] miRNA-503 Promotes Tumor Progression and Is Associated with Early Recurrence and Poor Prognosis in Human Colorectal Cancer. (2016)
  • Author(s): Noguchi T, Toiyama Y, Kitajima T, Imaoka H, Hiro J, Saigusa S, Tanaka K, Inoue Y, Mohri Y, Toden S, Kusunoki M
  • Journal Title: Oncology. Volume: 90(4) Issue: 4 Pages: 221-231
  • DOI: 10.1159/000444493
  • Peer Reviewed / Open Access
• [Journal Article] Elevated serum concentration of monocyte chemotactic protein 4 (MCP-4) as a novel non-invasive prognostic and predictive biomarker for detection of metastasis in colorectal cancer. (2016)
  • Author(s): Okugawa Y, Toiyama Y, Mohri Y, Tanaka K, Kawamura M, Hiro J, Araki T, Inoue Y, Miki C, Kusunoki M
  • Journal Title: J Surg Oncol. Volume: 114 Issue: 4 Pages: 483-489
  • DOI: 10.1002/jso.24335
  • Peer Reviewed
• [Journal Article] Circulating microRNA-1290 as a novel diagnostic and prognostic biomarker in human colorectal cancer (2016)
  • Author(s): Imaoka H, Toiyama Y, Fujikawa H, Hiro J, Saigusa S, Tanaka K, Inoue Y, Mohri Y, Mori T, Kato T, Toden S, Goel A, Kusunoki M.
  • Journal Title: Ann Oncol. Volume: 27(10） Issue: 10 Pages: 1879-1886
  • DOI: 10.1093/annonc/mdw279
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Diagnostic Potential of Cell-Free and Exosomal MicroRNAs in the Identification of Patients with High-Risk Colorectal Adenomas. (2016)
  • Author(s): Uratani R, Toiyama Y, Kitajima T, Kawamura M, Hiro J, Kobayashi M, Tanaka K, Inoue Y, Mohri Y, Mori T, Kato T, Goel A, Kusunoki M.
  • Journal Title: PLoS One. Volume: 11(10) Issue: 10 Pages: e0160722-e0160722
  • DOI: 10.1371/journal.pone.0160722
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] 大腸癌肝転移患者におけるHypoxia Inducible Factor 3A(HIF3)遺伝子内のLoss of heterozygosity(LOH)についての検討 (2017)
  • Author(s): 北嶋貴仁、問山裕二、奥川喜永、井出正造、近藤 哲、今岡裕基、廣純一郎、小林美奈子、楠 正人
  • Organizer: 第76回日本癌学会学術総会、横浜、2017.9.29
• [Presentation] 直腸癌に対する腹腔鏡下括約筋間切除・Coloplasty肛門吻合の手術手技と成績 (2016)
  • Author(s): 廣 純一郎, 井上 靖浩, 藤川 裕之, 沖上 正人, 今岡 裕基, 問山 裕二, 小林 美奈子, 荒木 俊光, 毛利 靖彦, 楠 正人
  • Organizer: 第78回日本臨床外科学会
  • Place of Presentation: 品川プリンスホテル(東京都、品川区)
  • Year and Date: 2016-11-24
• [Presentation] 膿瘍や瘻孔形成を伴った大腸憩室炎に対する腹腔鏡下手術の適応と成績 (2016)
  • Author(s): 廣 純一郎, 藤川 裕之, 問山 裕二, 井上 靖浩, 沖上 正人, 今岡 裕基, 小林 美奈子, 荒木 俊光, 毛利 靖彦, 楠 正人
  • Organizer: 第72回日本大腸肛門病学会
  • Place of Presentation: 伊勢サンアリーナ(三重県、伊勢市）
  • Year and Date: 2016-11-18
• [Presentation] 右側結腸癌に対する腹腔鏡下手術のリンパ節郭清と出血に対するポイントと対策 (2016)
  • Author(s): 廣 純一郎, 井上 靖浩, 藤川 裕之, 今岡 祐基, 沖上 正人, 問山 裕二, 奥川 喜永, 毛利 靖彦, 楠 正人
  • Organizer: 第71回日本消化器外科学会
  • Place of Presentation: アスティ徳島(徳島県、徳島市）
  • Year and Date: 2016-07-14