2021 Fiscal Year Final Research Report
Discovering tumor microenvironment of pancreatic cancer
| Project/Area Number |
19K09181
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55020:Digestive surgery-related
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| Research Institution | Kanagawa Cancer Center Research Institute |
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Principal Investigator |
Hiroshima Yukihiko 地方独立行政法人神奈川県立病院機構神奈川県立がんセンター(臨床研究所), 臨床研究所, 部長 (60718021)
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| Co-Investigator(Kenkyū-buntansha) |
黒滝 大翼 横浜市立大学, 医学部, 講師 (10568455)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 膵癌 / 微小環境 / PDX / オルガノイド / 遺伝子発現 / SMAD4 |
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| Outline of Final Research Achievements |
Cancer-stromal interactions have been recognized as important targets for cancer therapy. Here we studied 14 resected pancreatic cancer specimens (PDAC: 8, IPMA:6). Shotgun proteomics of the stromal lesion was performed, and identified 102 differentially expressed proteins in pancreatic cancer stroma. Next, we identified 1435 genes which were differentially expressed in pancreatic cancer cells, using TCGA and GTEx database. We applied these datasets to our in-house ligand-receptor database. Finally, we identified 8 key cancer-stromal-interaction targets for PDAC patients.
We studied 4 PDXs established from PDAC patients (2 had early recurrences and 2 had late recurrences). Only reads unambiguously classified as human were labeled “human” and used for further analyses. Next, we detected 28 DEGs, and “NFAT signaling cascade” was significantly enriched among the DEGs. Finally, we found that NFATc2/NFAT5 co-expression were independent prognostic factors for OS.
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| Free Research Field |
消化器外科、がんゲノム、がん薬物療法
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| Academic Significance and Societal Importance of the Research Achievements |
膵癌では癌の微小環境（TME）の増生が顕著であり、TMEの構造は癌細胞によって積極的に構築され、様々な側面から癌の進展（増殖、生存、浸潤、転移）を促進させていることが知られており、癌細胞とTMEとの相互作用は癌治療の新たな標的として注目を集めている。
本研究では、膵癌間質組織のマイクロダイセクション検体のプロテオーム解析データやPDXの解析データを使用し、癌細胞とTMEの発現分子を別々に検討し、インタラクトーム解析（独自の相互作用データベースに照会すること）により、真に標的とすべきシグナル伝達経路、相互作用が同定され、膵癌の新規治療薬の開発に重要な知見が得られたと考えられる。
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