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Metabolome analysis for early stage esophageal cancer

Research Project

Project/Area Number 20K22859
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0901:Oncology and related fields
Research InstitutionNational Cancer Center Japan

Principal Investigator

SAKASHITA SHINGO  国立研究開発法人国立がん研究センター, 先端医療開発センター, ユニット長 (40620638)

Project Period (FY) 2020-09-11 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords早期食道癌 / 低酸素環境 / 食道がん / メタボローム
Outline of Research at the Start

本研究の目的は、「食道がん病変における代謝微小環境」を検討し、腫瘍発生の初期における微小環境の影響を明らかにすることである。食道がん病変は初期から、ルゴール不染帯を示し、さらに、「酸素飽和度イメージング内視鏡」にて低酸素状態であることが確認されている。つまり、早期病変において既に代謝変化が起きている事が推定され、悪性化の一因と考えている。これを証明するため、早期食道癌から検体を採取し、病理学的な検討およびメタボローム解析を行う。研究の最終的な目標は、「腫瘍発生における微小環境の影響」を調べることであり、他のオミックス解析も必要であるが、本研究では、そのための基盤構築を行うことを目標としている。

Outline of Final Research Achievements

We hypothesized that the microenvironment, including metabolism, may form a predisposition for malignant transformation in the development of esophageal carcinoma. Using mucosectomy specimens of the esophagus, we analyzed the hypoxic environment of intraepithelial lesions (Tis-1a) and submucosal invasive lesions (T1b) using immunostaining, vascular, and hypoxic endoscopy. There were some markers that differed significantly between normal and tumor, and some markers that differed between Tis-1a and T1b, but in general, a large difference was found between T1a and T1b. Metabolomic analysis also revealed a number of metabolites that differ between T1a and T1b, and in esophageal cancer, the metabolic environment is different between non-invasive and invasive cancer.
The metabolic environment of esophageal cancer differs significantly between non-invasive and invasive cancers.

Academic Significance and Societal Importance of the Research Achievements

早期の食道癌において、リンパ節転移をしない非浸潤性の食道癌とリンパ節転移をきたしうる浸潤性の食道癌の低酸素環境、代謝環境が異なる事を示した。これは、食道癌の初期悪性化のメカニズム解明につながる可能性がある、非常に重要な発見である。特に、癌の発生に関わるとされるDriver mutationと思われるような共通する遺伝子異常が見つかっておらず、癌の発生は未だ謎に包まれている。今回の発見は、食道癌の予防という観点からも非常に重要な知見である。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (22 results)

All 2023 2022 2021

All Journal Article (22 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 22 results,  Open Access: 4 results)

  • [Journal Article] Tumor-identification method for predicting recurrence of early-stage lung adenocarcinoma using digital pathology images by machine learning2023

    • Author(s)
      Hattori Hideharu、Sakashita Shingo、Tsuboi Masahiro、Ishii Genichiro、Tanaka Toshiyuki
    • Journal Title

      Journal of Pathology Informatics

      Volume: 14 Pages: 100175-100175

    • DOI

      10.1016/j.jpi.2022.100175

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Requirement of image standardization for AI-based macroscopic diagnosis for surgical specimens of gastric cancer2023

    • Author(s)
      Sakashita Shingo、Sakamoto Naoya、Kojima Motohiro、Taki Tetsuro、Miyazaki Saori、Minakata Nobuhisa、Sasabe Maasa、Kinoshita Takahiro、Ishii Genichiro、Ochiai Atsushi
    • Journal Title

      Journal of Cancer Research and Clinical Oncology

      Volume: Online ahead of print Issue: 9 Pages: 6467-6477

    • DOI

      10.1007/s00432-022-04570-5

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Imaging Approach for Cervical Lymph Node Metastases from Unknown Primary Tumor2023

    • Author(s)
      Masuoka Sota、Hiyama Takashi、Kuno Hirofumi、Sekiya Kotaro、Sakashita Shingo、Kobayashi Tatsushi
    • Journal Title

      RadioGraphics

      Volume: 43 Issue: 3

    • DOI

      10.1148/rg.220071

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Clinicopathological significance of peritumoral alveolar macrophages in patients with resected early-stage lung squamous cell carcinoma2023

    • Author(s)
      Tanaka Y、Nakai T、Suzuki A、Kagawa Y、Noritake O、Taki T、Hashimoto H、Sakai T、Shibata Y、 Izumi H、Nosaki K、Udagawa H、Zenke Y、Matsumoto S、Yoh K、Miyazaki S、Sakamoto N、Sakashita S、Kojima M、Watanbe R、Tsuboi M、Goto K、Ishii G
    • Journal Title

      Cancer Immunology, Immunotherapy

      Volume: Online ahead of print Issue: 7 Pages: 2205-2215

    • DOI

      10.1007/s00262-023-03393-8

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Pathologic method for extracting good prognosis group in triple negative breast cancer after neoadjuvant chemotherapy.2022

    • Author(s)
      Eguchi Y, Nakai T, Kojima M, Wakabayashi M, Sakamoto N, Sakashita S, Miyazaki S, Taki T, Watanabe R, Watanuki R, Yamauchi C, Iwatani T, Mukohara T, Onishi T, Ishii G.
    • Journal Title

      Cancer Science

      Volume: 113(4) Issue: 4 Pages: 1507-1518

    • DOI

      10.1111/cas.15273

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prognostic impact of count of extratumoral lymphatic permeation in lung adenocarcinoma and its relation to the immune microenvironment.2022

    • Author(s)
      Niimi T, Nakai T, Aokage K, Tane K, Miyoshi T, Samejima J, Miyazaki S, Taki T, Sakamoto N, Sakashita S, Watanabe R, Kojima M, Suzuki K, Tsuboi M, Ishii G.
    • Journal Title

      Cancer Science

      Volume: 113(4) Issue: 4 Pages: 1497-1506

    • DOI

      10.1111/cas.15267

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Evaluation of Fluorescence Intensity and Antitumor Effect Using Real-Time Imaging in Photoimmunotherapy2022

    • Author(s)
      Takashima Kenji、Koga Yoshikatsu、Anzai Takahiro、Migita Kayo、Yamaguchi Toru、Ishikawa Akihiro、Sakashita Shingo、Yasunaga Masahiro、Yano Tomonori
    • Journal Title

      Pharmaceuticals

      Volume: 15 Issue: 2 Pages: 223-223

    • DOI

      10.3390/ph15020223

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Integrative analysis of non-small cell lung cancer patient-derived xenografts identifies distinct proteotypes associated with patient outcomes2022

    • Author(s)
      Mirhadi S、Tam S、Li Q、Moghal N、Pham N、Tong J、Golbourn B J.、Krieger J R.、Taylor P、Li M、Weiss J、Martins N.、Raghavan V、Mamatjan Y、Khan A A.、Cabanero M、Sakashita S、Huo K、 Agnihotri S、Ishizawa K、Waddell T K.、
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 36-50

    • DOI

      10.1038/s41467-022-29444-9

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Adult T-Cell Leukemia/Lymphoma With Extranodal Involvement of the Hypopharynx2022

    • Author(s)
      Fujimoto Shohei、Matsuura Kazuto、Nakamura Hirotaka、Sakashita Shingo、Hayashi Ryuichi
    • Journal Title

      Cureus

      Volume: 14 Pages: 22723-22723

    • DOI

      10.7759/cureus.22723

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dirty necrosis in renal cell carcinoma is associated with NETosis and systemic inflammation2022

    • Author(s)
      Kuroe Takashi、Watanabe Reiko、Morisue Ryo、Miyazaki Saori、Kojima Motohiro、Murata Shawhay Charles、Nakai Tokiko、Taki Tetsuro、Sakashita Shingo、Sakamoto Naoya、Matsubara Nobuaki、Masuda Hitoshi、Ushiku Tetsuo、Ishii Genichiro
    • Journal Title

      Cancer Medicine

      Volume: 12 Issue: 4 Pages: 4557-4567

    • DOI

      10.1002/cam4.5249

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The area of residual tumor predicts esophageal squamous cell carcinoma prognosis following neoadjuvant chemotherapy2022

    • Author(s)
      Adachi Masahiro、Aoyama Naoki、Kojima Motohiro、Sakamoto Naoya、Miyazaki Saori、Taki Tetsuro、Watanabe Reiko、Matsuura Kazuto、Kotani Daisuke、Kojima Takashi、Fujita Takeo、Tabuchi Keiji、Ishii Genichiro、Sakashita Shingo
    • Journal Title

      Journal of Cancer Research and Clinical Oncology

      Volume: Online ahead of print Issue: 8 Pages: 4663-4673

    • DOI

      10.1007/s00432-022-04366-7

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mitochondrial Aconitase ACO2 Links Iron Homeostasis with Tumorigenicity in Non-Small Cell Lung Cancer2022

    • Author(s)
      Mirhadi S、Zhang W、Pham N-A、Karimzadeh F、Pintilie M、Tong J、Taylor P、Krieger J、Pitcher B、Sykes J、Wybenga-G L、Fladd C、Xu J、Wang T、Cabanero M、Li M、Weiss J、Sakashita S、 Zaslaver O、Yu M、Caudy A.、St-Pierre J、H、Kislinger T、Liu G、Shepherd Frances A.、Tsao Ming-Sound、Moran F.
    • Journal Title

      Molecular Cancer Research

      Volume: 21 Issue: 1 Pages: 36-50

    • DOI

      10.1158/1541-7786.mcr-22-0163

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Clinicopathological features and prognostic impact of dirty necrosis in metastatic lung cancers from the colon and rectum2022

    • Author(s)
      Konishi Yasuhito、Taki Tetsuro、Nakai Tokiko、Kuroe Takashi、Morisue Ryo、Miyoshi Tomohiro、Tane Kenta、Samejima Joji、Aokage Keiju、Miyazaki Saori、Sakamoto Naoya、Sakashita Shingo、Watanabe Reiko、Kojima Motohiro、Suzuki Kenji、Tsuboi Masahiro、Ishii Genichiro
    • Journal Title

      Cancer Science

      Volume: 114 Issue: 5 Pages: 2169-2177

    • DOI

      10.1111/cas.15647

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The impact of tertiary lymphoid structures on clinicopathological, genetic and gene expression characteristics in lung adenocarcinoma2022

    • Author(s)
      Tamiya Y、Nakai T、Suzuki A、Mimaki S、Tsuchihara K、Sato K、Yoh K、Matsumoto S、Zenke Y、 Nosaki K、Izumi H、Shibata Y、Sakai T、Taki T、Miyazaki S、Watanabe R、Sakamoto N、Sakashita S、Kojima M、Hashimoto N、Tsuboi M、Goto K、Ishii G
    • Journal Title

      Lung Cancer

      Volume: 174 Pages: 125-132

    • DOI

      10.1016/j.lungcan.2022.11.001

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical Analysis of Common Cancer Antigens in Head and Neck Squamous Cell Carcinoma2022

    • Author(s)
      MORISHITA YOHEI、TAKENOUCHI KAZUMASA、SAKASHITA SHINGO、MATSUURA KAZUTO、HAYASHI RYUICHI、NAKATSURA TETSUYA
    • Journal Title

      Anticancer Research

      Volume: 42 Issue: 12 Pages: 5751-5761

    • DOI

      10.21873/anticanres.16082

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A case of Epstein?Barr virus-positive mucocutaneous ulcer of the hypopharynx: a mimicker of hypopharyngeal squamous cell carcinoma2021

    • Author(s)
      Masuoka Sota、Hiyama Takashi、Kuno Hirofumi、Morishita Yohei、Sakashita Shingo、Kobayashi Tatsushi
    • Journal Title

      International Cancer Conference Journal

      Volume: 11 Issue: 1 Pages: 71-74

    • DOI

      10.1007/s13691-021-00523-w

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Assessing therapy response in patient-derived xenografts2021

    • Author(s)
      Ortmann J, Rampasek L, Tai E, Mer AS, Shi R, Stewart EL, Mascaux C, Fares A, Pham NA, Beri G, Eeles C, Tkachuk D, Ho C, Sakashita S, Weiss J, Jiang X, Liu G, Cescon DW, O'Brien CA, Guo S, Tsao MS, Haibe-Kains B, Goldenberg A.
    • Journal Title

      Science Translational Medicine

      Volume: 13 Issue: 620 Pages: 620-620

    • DOI

      10.1126/scitranslmed.abf4969

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Human papillomavirus-related multiphenotypic sinonasal carcinoma2021

    • Author(s)
      Morishita Yohei、Sakashita Shingo、Tomioka Toshifumi、Okano Wataru、Shinozaki Takeshi、Higashino Takuya、Matsuura Kazuto、Hayashi Ryuichi
    • Journal Title

      Auris Nasus Larynx

      Volume: 21 Issue: 1 Pages: 255-8

    • DOI

      10.1016/j.anl.2021.10.008

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activation of a Cryptic Splice Site of <i>GFAP</i> in a Patient With Adult-Onset Alexander Disease2021

    • Author(s)
      Amano Eiichiro、Yoshida Tomokatsu、Mizuta Ikuko、Oyama Jun、Sakashita Shingo、Ueyama Syunsuke、Machida Akira、Yokota Takanori
    • Journal Title

      Neurology Genetics

      Volume: 7 Issue: 6

    • DOI

      10.1212/nxg.0000000000000626

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Integrative RNA-Seq and H3 Trimethylation ChIP-Seq Analysis of Human Lung Cancer Cells Isolated by Laser-Microdissection2021

    • Author(s)
      Ong Quang、Sakashita Shingo、Hanawa Emi、Kaneko Naomi、Noguchi Masayuki、Muratani Masafumi
    • Journal Title

      Cancers

      Volume: 13 Issue: 7 Pages: 1719-1719

    • DOI

      10.3390/cancers13071719

    • NAID

      120007180741

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] Prognostic impact of extranodal extension in patients with pN1?N2 lung adenocarcinoma2021

    • Author(s)
      Nomura Kotaro、Aokage Keiju、Nakai Tokiko、Sakashita Shingo、Miyoshi Tomohiro、Tane Kenta、Samejima Joji、Suzuki Kenji、Tsuboi Masahiro、Ishii Genichiro
    • Journal Title

      Journal of Cancer Research and Clinical Oncology

      Volume: 147 Issue: 12 Pages: 3699-3707

    • DOI

      10.1007/s00432-021-03608-4

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Journal Article] An autopsy case of aortic dissection due to giant cell arteritis2021

    • Author(s)
      Sakashita Mai、Sakashita Shingo、Uesugi Noriko、Tokunaga Chiho、Hiramatsu Yuji、Noguchi Masayuki、Sakamoto Noriaki
    • Journal Title

      Pathology International

      Volume: 71 Issue: 3 Pages: 204-209

    • DOI

      10.1111/pin.13046

    • Related Report
      2021 Research-status Report
    • Peer Reviewed

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Published: 2020-09-29   Modified: 2024-01-30  

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