Pathological investigation of iron regulatory protein in the progression of hepatobiliary malignancy
| Project/Area Number |
15K08347
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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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| Research Field |
Human pathology
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| Research Institution | Saga University |
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Principal Investigator |
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| Project Period (FY) |
2015-04-01 – 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 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 肝細胞癌 / 鉄代謝 / トランスフェリン受容体 / 活性酸素 / 発がん / 肝細胞がん / 酸化ストレスう / Hepcidin |
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| Outline of Final Research Achievements |
Hepatocellular carcinoma (HCC) is the second leading cause of cancer mortality worldwide. An excess of iron in liver tissue causes oxidative stress, leading to hepatocellular carcinogenesis. Iron metabolism, which is regulated by a complex mechanism, is important for cancer cell survival. The aim of this study is to clarify the role of iron regulatory protein in the progression of HCC and in patient outcome. High expression of TFR1 in HCC was associated with liver cirrhosis (p<0.0001), higher alpha-fetoprotein (AFP) (p<0.0001), smaller tumor size (p=0.0022), poor histological differentiation (p<0.0001) and morphological features (p<0.0001). Multivariate analysis for both overall survival and recurrence-free survival indicated that high TFR1 expression was a significant prognostic factor for poor outcome. TFR1 overexpression suggests a higher risk of recurrence and death in HCC patients following liver resection.
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| Academic Significance and Societal Importance of the Research Achievements |
肝細胞癌(HCC)は有効な治療法の確立が望まれている腫瘍である。肝臓は鉄の貯蔵を担う臓器であり、鉄の蓄積は酸化ストレスを介した肝発がんを促進するする。鉄の代謝にかかわる遺伝子は多数あり複雑なメカニズムによって鉄代謝は制御され、がん細胞においても鉄の代謝は細胞の生存にとって極めて重要である。今回、鉄代謝の重要なたんぱく質であるトランスフェリン受容体１(TFR1)の高い発現がHCCの腫瘍形成や脱分化に関連し、生存にもかかわることが明らかになった。TFR1の発現はほかの悪性腫瘍でも高い発現が確認されており、がんの治療も期待されているたんぱく質である。
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Report
(5 results)
Research Products
(3 results)
