Research of useful molecular markers for hepatocellular carcinoma subclassfication and the application to pathological diagnosis
| Project/Area Number |
17K15655
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Human pathology
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 肝細胞癌 / サブクラス分類 / 腫瘍悪性度 / 人体病理学 |
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| Outline of Final Research Achievements |
Hepatocellular carcinoma (HCC) were classified into three groups based on the intensity and ratio of ERK nuclear expression. ERK-activated hepatocellular carcinoma is poorly differentiated with high serum alpha-fetoprotein levels, high vascular invasion, and high expression of Cytokeratin19 and SALL4, c-MET, ki-67, which is associated with cell proliferation and tumor malignancy.
Quantitative analysis of intratumoral collagen and elastin fibers in HCC and clinico-pathoradiological study showed that stromal fiber-rich HCC were significantly associated with the biliary/stem cell markers-positive HCC subtype and likely represent a distinct clinico-pathoradiological entity.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果からは、ERK活性化が肝細胞癌の予後因子の一つであることが判明し、線維成分に富む肝細胞癌は、臨床病理放射線学的に特徴的な一群として認識されることが分かった。いずれも高悪性度とされる胆管上皮/幹細胞マーカー陽性群に関連しており、すぐに日常診断時に用いるのは難しいものの、肝細胞癌悪性度に関連する重要な因子である。さらに、肝細胞癌治療薬として用いられるsorafenib によりERK リン酸化および細胞増殖能が抑制されることも報告しており、将来的に治療選択に繋がる可能性が考えられた。
肝細胞癌のサブクラス分類は腫瘍悪性度を推し量ることができ、患者の治療選択や予後予測に重要であると考えられた。
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Report
(5 results)
Research Products
(10 results)
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[Journal Article] Activation of extracellular signal-regulated kinase is associated with hepatocellular carcinoma with aggressive phenotypes.2020
Author(s)
Minagawa T, Yamazaki K, Masugi Y, Tsujikawa H, Ojima H, Hibi T, Abe Y, Yagi H, Kitago M, Shinoda M, Itano O, Kitagawa Y, Sakamoto M.
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Journal Title
Hepatology Reserch
Volume: 2020 Mar;50(3)
Issue: 3
Pages: 353-364
DOI
Related Report
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[Journal Article] Quantification of intratumoral collagen and elastin fibers within hepatocellular carcinoma tissues finds correlations with clinico-patho-radiological features.2019
Author(s)
Maehara J, Masugi Y, Abe T, Tsujikawa H, Kurebayashi Y, Ueno A, Ojima H, Okuda S, Jinzaki M, Shinoda M, Kitagawa Y, Oda Y, Honda H, Sakamoto M.
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Journal Title
Hepatology Reserch
Volume: 2019 Dec 30.
Issue: 5
Pages: 607-619
DOI
Related Report
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