Integrative analysis to identify the unique microRNA-mRNA regulatory network in EGFR-mutated lung adenocarcinoma: toward precision medicine
Project/Area Number |
16K08679
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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 |
Research Field |
Human pathology
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Research Institution | Japanese Foundation for Cancer Research |
Principal Investigator |
KENTARO INAMRUA 公益財団法人がん研究会, がん研究所 病理部, 主任研究員 (40442545)
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Project Period (FY) |
2016-04-01 – 2019-03-31
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Project Status |
Completed (Fiscal Year 2018)
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Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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Keywords | マイクロRNA / メッセンジャーRNA / ドライバー遺伝子 / マイクロアレイ / 網羅的遺伝子発現解析 / 統合解析 / 肺がん / 腺がん / 肺癌 / 腺癌 / 人体病理学 |
Outline of Final Research Achievements |
In lung adenocarcinoma, various mutations that drive cancer progression have emerged as druggable molecular targets. Among them, EGFR mutation is the most prevalent genetic alterations. EGFR-mutated lung adenocarcinoma is characterized by a distinct oncogenic pathway with unique microRNA-mRNA interactions. We investigated both microRNA and mRNA expression profiles using microarrays in 155 cases of lung adenocarcinoma. An integrative analysis of microRNA and mRNA expression revealed a list of microRNA-mRNA interactions in EGFR-mutated tumors. A network structural analysis provided a comprehensive view of the complex microRNA-mRNA interactions, including interactions of miR-500a-3p, miR-502-3p, and miR-652-3p with MUC4. Overall, this observational study provides insight into the unique microRNA-mRNA regulatory network in EGFR-mutated tumors. Our findings, if validated, would inform future research examining the interplay between microRNAs and mRNAs in EGFR-mutated lung adenocarcinoma.
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Academic Significance and Societal Importance of the Research Achievements |
EGFR変異は日本人の肺がんにおいて最も頻度の高いドライバー遺伝子異常である。一方、マイクロRNAはメッセンジャーRNAとの相互作用を介して発がん・がん進展において重要な働きをすることが知られている。本研究では、網羅的統合発現解析により、EGFR変異肺がんに特徴的なマイクロRNA-メッセンジャーRNA相互作用をネットワーク化した。本研究で同定されたEGFR変異肺がんに特徴的なマイクロRNA・メッセンジャーRNA間の相互作用は、EGFR変異肺がんの発がん・がん進展のメカニズムを理解する上で有用であると考えられる。将来的にはマイクロRNAをターゲットとする診断治療戦略に応用されることが期待される。
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Report
(4 results)
Research Products
(50 results)
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[Journal Article] Prognostic Effect of Lymphovascular Invasion on TNM Staging in Stage I Non-Small-cell Lung Cancer.2018
Author(s)
Noma D, Inamura K, Matsuura Y, Hirata Y, Nakajima T, Yamazaki H, Hirai Y, Ichinose J, Nakao M, Ninomiya H, Mun M, Nakagawa K, Masuda M, Ishikawa Y, Okumura S.
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Journal Title
Clin Lung Cancer
Volume: 19(1)
Issue: 1
Pages: e109-e122
DOI
Related Report
Peer Reviewed
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[Journal Article] Genetic mechanisms of immune evasion in colorectal cancer.2018
Author(s)
Grasso CS, Giannakis M, Wells DK, Hamada T, Mu XJ, Quist M, Nowak JA, Nishihara R, Qian ZR, Inamura K, Morikawa T, Nosho K, et al.
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Journal Title
Cancer Discov.
Volume: 印刷中
Issue: 6
Pages: 730-749
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Osteosarcoma arising in fibrous dysplasia, confirmed by mutational analysis of GNAS gene.2018
Author(s)
Sugiura Y, Kanda H, Motoi N, Nomura K, Inamura K, Okada E, Matsumoto H, Shimoji T, Matsumoto S, Nakayama J, Takazawa Y, Ishikawa Y, Machinami R.
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Journal Title
Pathol Res Pract.
Volume: 214(2)
Issue: 2
Pages: 318-324
DOI
Related Report
Peer Reviewed
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[Journal Article] Association of tumor TROP2 expression with prognosis varies among lung cancer subtypes.2017
Author(s)
Inamura K, Yokouchi Y, Kobayashi M, Ninomiya H, Sakakibara R, Subat S, Nagano H, Nomura K, Okumura S, Shibutani T, Ishikawa Y.
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Journal Title
Oncotarget
Volume: 8(17)
Pages: 28725-28735
Related Report
Peer Reviewed / Open Access
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[Journal Article] Tumor B7-H3 (CD276) expression and smoking history in relation to lung adenocarcinoma prognosis.2017
Author(s)
Inamura K, Yokouchi Y, Kobayashi M, Sakakibara R, Ninomiya H, Subat S, Nagano H, Nomura K, Okumura S, Shibutani T, Ishikawa Y.
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Journal Title
Lung Cancer
Volume: 103
Pages: 44-51
DOI
Related Report
Peer Reviewed
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[Journal Article] Tumor PDCD1LG2 (PD-L2) Expression and the Lymphocytic Reaction to Colorectal Cancer.2017
Author(s)
Masugi Y, Nishihara R, Hamada T, Song M, da Silva A, Kosumi K, Gu M, Shi Y, Li W, Liu L, Nevo D, Inamura K, Cao Y, Liao X, Nosho K, Chan AT, Giannakis M, Bass AJ, Hodi FS, Freeman GJ, Rodig SJ, Fuchs CS, Qian ZR, Nowak JA, Ogino S.
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Journal Title
Cancer Immunol Res.
Volume: 5(11)
Issue: 11
Pages: 1046-1055
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Association Between Inflammatory Diet Pattern and Risk of Colorectal Carcinoma Subtypes Classified by Immune Responses to Tumor.2017
Author(s)
Liu L, Nishihara R, Qian ZR, Tabung FK, Nevo D, Zhang X, Song M, Cao Y, Mima K, Masugi Y, Shi Y, da Silva A, Twombly T, Gu M, Li W, Hamada T, Kosumi K, Inamura K, Nowak JA, Drew DA, Lochhead P, Nosho K, Wu K, Wang M, Garrett WS, Chan AT, Fuchs CS, Giovannucci EL, Ogino S.
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Journal Title
Gastroenterology.
Volume: 153(6)
Issue: 6
Pages: 1517-1530.e14
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Tumour CD274 (PD-L1) expression and T cells in colorectal cancer.2017
Author(s)
Masugi Y, Nishihara R, Yang J, Mima K, da Silva A, Shi Y, Inamura K, Cao Y, Song M, Nowak JA, Liao X, Nosho K, Chan AT, Giannakis M, Bass AJ, Hodi FS, Freeman GJ, Rodig S, Fuchs CS, Qian ZR, Ogino S.
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Journal Title
Gut
Volume: 印刷中
Issue: 8
Pages: 1463-1473
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Association Between Somatostatin Receptor Expression and Clinical Outcomes in Neuroendocrine Tumors.2016
Author(s)
Qian ZR, Li T, Ter-Minassian M, Yang J, Chan JA, Brais LK, Masugi Y, Thiaglingam A, Brooks N, Nishihara R, Bonnemarie M, Masuda A, Inamura K, Kim SA, Mima K, Sukawa Y, Dou R, Lin X, Christiani DC, Schmidlin F, Fuchs CS, Mahmood U, Ogino S, Kulke MH.
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Journal Title
Pancreas
Volume: 45
Issue: 10
Pages: 1386-1393
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Thymic oncocytic carcinoid with a markedly elevated level of maximum SUV.2016
Author(s)
Noma D, Inamura K, Mun M, Terauchi T, Matsuura Y, Nakao M, Ninomiya H, Nakagawa K, Masuda M, Okumura S, Ishikawa Y.
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Journal Title
Pathol Int.
Volume: 66
Issue: 10
Pages: 593-595
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Regular Aspirin Use Associates With Lower Risk of Colorectal Cancers With Low Numbers of Tumor-Infiltrating Lymphocytes.2016
Author(s)
Cao Y, Nishihara R, Qian ZR, Song M, Mima K, Inamura K, Nowak JA, Drew DA, Lochhead P, Nosho K, Morikawa T, Zhang X, Wu K, Wang M, Garrett WS, Giovannucci EL, Fuchs CS, Chan AT, Ogino S.
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Journal Title
Gastroenterology
Volume: 151
Issue: 5
Pages: 879-892
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Genomic Correlates of Immune-Cell Infiltrates in Colorectal Carcinoma.2016
Author(s)
Giannakis M, Mu XJ, Shukla SA, Qian ZR, Cohen O, Nishihara R, Bahl S, Cao Y, Amin-Mansour A, Yamauchi M, Sukawa Y, Stewart C, Rosenberg M, Mima K, Inamura K, Nosho K, Nowak JA, Lawrence MS, Giovannucci EL, Chan AT, Ng K, Meyerhardt JA, Van Allen EM, Getz G, Gabriel SB, Lander ES, Wu CJ, Fuchs CS, Ogino S, Garraway LA.
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Journal Title
Cell Rep.
Volume: 15
Issue: 4
Pages: 857-865
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Marine ω-3 Polyunsaturated Fatty Acid Intake and Risk of Colorectal Cancer Characterized by Tumor-Infiltrating T Cells.2016
Author(s)
Song M, Nishihara R, Cao Y, Chun E, Qian ZR, Mima K, Inamura K, Masugi Y, Nowak JA, Nosho K, Wu K, Wang M, Giovannucci E, Garrett WS, Fuchs CS, Ogino S, Chan AT.
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Journal Title
JAMA Oncol.
Volume: 2
Issue: 9
Pages: 1197-1206
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Body mass index and risk of colorectal cancer according to tumor lymphocytic infiltrate.2016
Author(s)
Hanyuda A, Ogino S, Qian ZR, Nishihara R, Song M, Mima K, Inamura K, Masugi Y, Wu K, Meyerhardt JA, Chan AT, Fuchs CS, Giovannucci EL, Cao Y.
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Journal Title
Int J Cancer
Volume: 139
Issue: 4
Pages: 854-868
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] Sakakibara R, Ninomiya H, Inamura K, Nakashima Y, Okumura S, Ishikawa Y. Update in theDiagnosis of neuroendocrine tumor and its prognostic value.2018
Author(s)
Sakakibara R, Ninomiya H, Inamura K, Nakashima Y, Okumura S, Ishikawa Y.
Organizer
The 5-th Asian-Australasian Pulmonary Pathology Society (AAPPS) annual conference
Related Report
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[Presentation] Tumor B7-H3 (CD276) protein expression, smoking history, and survival in lung adenocarcinoma patients.2016
Author(s)
Inamura K, Yokouchi Y, Kobayashi M, Sakakibara R, Ninomiya H, Subat S, Nagano H, Nomura K, Okumura S, Shibutani T, Ishikawa Y.
Organizer
17th World conference on lung cancer
Place of Presentation
Vienna, Austria
Year and Date
2016-12-04
Related Report
Int'l Joint Research
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[Presentation] Insulinoma-Associated 1 (INSM1) immunohistochemical expression in lung neuroendocrine tumors.2016
Author(s)
Sakakibara R, Inamura K, Ninomiya H, Shigematsu Y, Kakita T, Noma D, Hirata Y, Matsuura Y, Nakao M, Mun M, Nishio M, Okumura S, Ishikawa Y.
Organizer
17th World conference on lung cancer
Place of Presentation
Vienna, Austria
Year and Date
2016-12-04
Related Report
Int'l Joint Research
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[Presentation] B7-H3 (CD276) expression, smoking history, and patient survival in lung adenocarcinoma.2016
Author(s)
Inamura K, Kobayashi M, Sakakibara R, Ninomiya H, Subat S, Nagano H, Nomura K, Okumura S, Ishikawa Y.
Organizer
75th Annual Meeting of the Japanese Cancer Association
Place of Presentation
Yokohama
Year and Date
2016-10-06
Related Report
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[Presentation] Asthma and risk of colorectal cancer according to tumor immunity and molecular subtypes.2016
Author(s)
Li Y, Song M, Nishihara R, Qian ZR, Varraso R, Inamura K, Masugi Y, Giovannucci EL, Wang M, Camargo CA, Fuchs CS, Chan AT, Ogino S, Cao Y.
Organizer
AACR Special Conference: Colorectal Cancer: From Initiation to Outcomes
Place of Presentation
Tampa, FL, USA
Year and Date
2016-09-17
Related Report
Int'l Joint Research
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[Presentation] Aspirin Use and Risk of Colorectal Cancer According to Tumor Immunity Status.2016
Author(s)
Cao Y, Nishihara R, Qian ZR, Song M, Mima K, Inamura K, Nowak J, Drew D, Lochhead P, Nosho K, Morikawa T, Zhang X, Wu K, Wang M, Garrett WS, Giovannucci E, Fuchs CS, Ogino S, Chan AT.
Organizer
Digestive Disease Week
Place of Presentation
San Diego, CA, USA
Year and Date
2016-05-22
Related Report
Int'l Joint Research
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[Presentation] B7-H3 protein expression and patient survival according to smoking status in lung adenocarcinoma2016
Author(s)
稲村健太郎, 横内友祐, 小林真季, 河内洋, 二宮浩範, ソバティ・ソフィア, 本田小吉, 小坂俊幸, 渋谷朋子, 石川雄一.,
Organizer
第105回日本病理学会総会
Place of Presentation
仙台
Year and Date
2016-05-12
Related Report
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[Presentation] Marine ω-3 polyunsaturated fatty acid intake and risk of colorectal cancer according to tumor-infiltrating T cells.2016
Author(s)
Song M, Nishihara R, Cao Y, Chun E, Qian ZR, Mima K, Inamura K, Masugi Y, Nowak J, Nosho K, Wu K, Wang M, Giovannucci E, Garrett WS, Fuchs CS, Ogino S, Chan AT.
Organizer
The AACR 107th Annual Meeting 2016
Place of Presentation
New Orleans, LA, USA
Year and Date
2016-04-16
Related Report
Int'l Joint Research
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