Genetic background factors and local cancer microenvironmental factors determining tumor immune response in colorectal cancer
Project/Area Number |
18K08649
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 55020:Digestive surgery-related
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Research Institution | Kyushu University |
Principal Investigator |
Kuroda Yosuke 九州大学, 大学病院, 特別教員 (10779995)
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Co-Investigator(Kenkyū-buntansha) |
三森 功士 九州大学, 大学病院, 教授 (50322748)
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | 腫瘍免疫応答 / コピー数変異 / TCRレパートリー / 腫瘍抗原 / 大腸がん再発 / 大腸がん / ポリジェニックスコア / 遺伝子多型 / 発がん / 予後再発 / ゲノム変異 / 数理学的統合解析 / TCRレパトア / アームコピー数変異 / 突然変異 / ネオアンチゲン |
Outline of Final Research Achievements |
The presence or absence of recurrence of colorectal cancer is thought to be due to differences in tumor immune responses in the primary tumor. We performed multi-region WES on 10 cases of early stage (stage I or II) colorectal tumors that recurred postoperatively. The results showed that arm-level CNAs (multiplicity) in colorectal cancer cases were significantly more common in primary tumors of recurrence-positive cases than in non-recurrent primary tumors (p < 2.2e-16), and that there was an inverse correlation between the number of SNVs and arm-level CANs (chromosomes 7p, 7q, 20p, and 20q). We found an inverse correlation between the number of SNVs and arm-level CNAs (chromosomes 7p, 7q, 20p, and 20q) in 409 TCGA colorectal cancer cases. CYT was also lower in recurrence-positive (n = 40) compared to primary tumors (n = 232) and recurrence-negative (n = 232). Pre-metastatic sites before the initiation of the metastasis can prevent cancer metastasis in the future.
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Academic Significance and Societal Importance of the Research Achievements |
われわれはコピー数異常(CNA)が、原発巣における早期から進行した腫瘍へのがん進化を促進する最も重要な選択圧であることを明らかにした。進行がんにおける中立進化の過程では、がん細胞のネオアンチゲン(NAG)の減少と細胞傷害性T細胞のTCRレパトア多様性が、クローナルなCNAやいくつかのドライバー変異とともに、原発部位から再発部位への術後再発発症を規定していた。本助成をいただき明らかにした結果に基づき、転移プロセスの開始前に、転移前の部位でCTLを活性化することは、今後がんの転移を防ぐことが可能になることが期待され、医療費逓減が求められている今日、社会的意義は大きい。
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Report
(4 results)
Research Products
(57 results)
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[Journal Article] Prognostic Significance of PD-1, PD-L1 and CD8 Gene Expression Levels in Gastric Cancer.2020
Author(s)
Ito S, Masuda T, Noda M, Hu Q, Shimizu D, Kuroda Y, Eguchi H, Tobo T, Utsunomiya T, Mimori K.
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Journal Title
Oncology.
Volume: 98(7)
Issue: 7
Pages: 501-511
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] SF3B4 Plays an Oncogenic Role in Esophageal Squamous Cell Carcinoma.2020
Author(s)
Kidogami S, Iguchi T, Sato K, Yoshikawa Y, Hu Q, Nambara S, Komatsu H, Ueda M, Kuroda Y, Masuda T, Mori M, Doki Y, Mimori K.
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Journal Title
Anticancer Res.
Volume: 40(5)
Issue: 5
Pages: 2941-2946
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] KIF15 Expression in Tumor-associated Monocytes Is a Prognostic Biomarker in Hepatocellular Carcinoma.2020
Author(s)
Kitagawa A, Masuda T, Takahashi J, Tobo T, Noda M, Kuroda Y, Hu Q, Kouyama Y, Kobayashi Y, Kuramitsu S, Sato K, Fujii A, Yoshikawa Y, Wakiyama H, Shimizu D, Tsuruda Y, Eguchi H, Doki Y, Mori M, Mimori K.
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Journal Title
Cancer Genomics Proteomics.
Volume: 17(2)
Issue: 2
Pages: 141-149
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] GTF2IRD1 on chromosome 7 is a novel oncogene regulating the tumor-suppressor gene TGFβR2 in colorectal cancer.2020
Author(s)
Nambara S, Masuda T, Kobayashi Y, Sato K, Tobo T, Koike K, Noda M, Ogawa Y, Kuroda Y, Ito S, Eguchi H, Sugimachi K, Mimori K.
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Journal Title
Cancer Sci.
Volume: 111(2)
Issue: 2
Pages: 343-355
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Novel oncogene 5MP1 reprograms c-Myc translation initiation to drive malignant phenotypes in colorectal cancer.2019
Author(s)
Sato K, Masuda T, Hu Q, Tobo T, Gillaspie S, Niida A, Thornton M, Kuroda Y, Eguchi H, Nakagawa T, Asano K, Mimori K.
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Journal Title
EBioMedicine.
Volume: 44
Pages: 387-402
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A clinical trial of somatic and germline analyses for healthy longevity in a postoperative cancer patient.2019
Author(s)
Hayashi N, Kuroda Y, Saito T, Tsuruda Y, Niida A, Otsu H, Eguchi H, Masuda T, Suzuki Y, Natsugoe S, Mimori K.
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Journal Title
Surg Today.
Volume: Epub
Issue: 9
Pages: 738-747
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Oncogenic splicing abnormalities induced by DEAD-Box Helicase 56 amplification in colorectal cancer.2019
Author(s)
Kouyama Y, Masuda T, Fujii A, Ogawa Y, Sato K, Tobo T, Wakiyama H, Yoshikawa Y, Noda M, Tsuruda Y, Kuroda Y, Eguchi H, Ishida F, Kudo SE, Mimori K.
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Journal Title
Cancer Sci.
Volume: 110(10)
Issue: 10
Pages: 3132-3144
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A temporal shift of the evolutionary principle shaping intratumor heterogeneity in colorectal cancer2018
Author(s)
Saito T, Niida A, Uchi R, Hirata H, Kodama M, Okimoto T, Murakami K, Suzuki Y, Ogawa S, Miyano S, Mimori K, et al.
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Journal Title
Nature Communications
Volume: 9
Issue: 1
Pages: 2884-2884
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Identification of ARL4C as a Peritoneal Dissemination-Associated Gene and Its Clinical Significance in Gastric Cancer.2018
Author(s)
Hu Q, Masuda T, Sato K, Tobo T, Nambara S, Kidogami S, Hayashi N, Kuroda Y, Ito S, Eguchi H, Saeki H, Oki E, Maehara Y, Mimori K
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Journal Title
Ann Surg Oncol
Volume: 25(3)
Issue: 3
Pages: 745-753
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Clinical significance of GET4 expression in colorectal cancer.2019
Author(s)
Kensuke Koike, Takaaki Masuda, Kuniaki Sato, Yushi Motomura, Junuchi Takahashi, Dai Shimizu, Shotaro Kuramitsu, Atsushi Fujii, Akihiro Kitagawa, Miwa Noda, Yusuke Tsuruda, Hajime Otsu, Yousuke Kuroda, Hidetoshi Eguchi, Takashi Nakagawa, Koshi Mimori.
Organizer
AACR Annual Meeting 2019
Related Report
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[Presentation] Clinical significance of Fanconi anemia complementation group E (FANCE) DNA repair-related gene expression in hepatocellular carcinoma2019
Author(s)
Junichi Takahashi, Takaaki Masuda, Yosuke Kuroda, Akihiro Kitagawa, Yushi Motomura, Kensuke Koike, Dai Shimizu, Shotaro Kuramitsu,Atsushi Fujii, Miwa Noda, Kuniaki Sato, Yusuke Tsuruda, Hajime Otsu, Hidetoshi Eguchi, Keishi Sugimachi, Masaki Mori, Koshi Mimori.
Organizer
AACR Annual Meeting 2019
Related Report
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[Presentation] Clinical significance of eif5 mimic protein 1 in pancreatic cancer.2019
Author(s)
Yushi Motomura, Takaaki Masuda, Kuniaki Sato, Atsushi Fujii, Akihiro Kitagawa, Hiroaki Wakiyama, Kensuke Koike, Junichi Takahashi, Dai Shimizu, Shitaro Kuramitsu, Miwa Noda, Yusuke Tsuruda, Hajime Otsu, Yosuke Kuroda, Hidetoshi Eguchi, Katsumi Sakamoto, Msakazu Hirakawa, Hiroshi Honda, Koshi Mimori.
Organizer
AACR Annual Meeting 2019
Related Report
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[Presentation] Circulating exosomal miR-203 is associated with metastasis via inducing tumor-associated macrophages in colorectal cancer2018
Author(s)
D Shimizu, T Masuda, Y Takano, H Iinuma, R Yamaguchi, K Sato, T Tobo, H Hirata, Y Kuroda, S Nambara, N Hayashi, T Iguchi, S Ito, H Eguchi, T Ochiya, K Yanaga, S Miyano, K Mimori.
Organizer
AACR Annual Meeting 2018
Related Report
Int'l Joint Research
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