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発現プロテオミクスに基づいた肝癌再発予測システムの開発

基于表达蛋白质组学的肝癌复发预测系统的开发

基本信息

批准号：
15659315
负责人：
岡正朗
金额：
$ 2.11万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Exploratory Research
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15659315/
关键词：
肝細胞癌プロテオミクス heat shock protein 特異的蛋白再発予測

项目摘要

【背景と目的】HCV関連肝細胞癌(HCV-HCC)に対して二次元電気泳動(2DE)と質量分析(MALDI-TOF/MS)を用いたプロテオーム解析を行い、発癌や進行に関与する蛋白の検討および臨床的に血清学的診断マーカーとなり得る血中抗体の検討を行った。【対象】当院にて初回治療として外科的肝切除術を施行したHCV-HCC26例を対象とした。内訳は男性16人、女性10人。組織型は高分化型6例、中分化型15例、低分化型5例。血中抗体の検討にはこのうちの10例の血清を使用した。【方法】すべての標本から癌組織と非癌組織をペアで採取し、それぞれから蛋白を抽出。抽出された蛋白を2DEにて分離し、その発現パターンを癌組織と非癌組織の間で比較した後、両者で発現差のある蛋白スポットをMALDI-TOF/MSにて同定した。また、癌組織中の蛋白と患者血清を反応させ、血中に発現する自己抗体の存在を調べた。【結果】癌組織では非癌組織と比較して、増加している蛋白が11種類、減少している蛋白が8種類確認された。増加している蛋白のうち4種類はHSP70familyに属する蛋白であり、これら4つの蛋白は相関して同時に増加していた。また、同じく癌組織で増加する蛋白の中にglutamine synthetase (GS)とalpha enolase (ENOA)が認められた。GSは高分化型HCCで増加する傾向があった。一方ENOAは低分化型HCCにおいて増加しており、その発現レベルは腫瘍の大きさや脈管浸潤の有無と関連性が認められた。また、患者血清にはHSP70、peroxiredoxin、superoxide dismutaseに対する抗体が健常人血清と比較して有意に発現していた。【結語】今回同定された蛋白はHCV-HCCの発癌過程において重要な役割を担うと思われ、血中抗体は将来的に診断マーカーとして臨床応用できる可能性があると思われた。

[background] HCV was used to detect liver cancer (HCV-HCC). Two-dimensional electrophoresis (2DE) quantitative analysis (MALDI-TOF/MS) was used to analyze liver cancer cells. The serum samples of the cancer patients were detected by serological assay and the serum antibodies of the cancer patients were detected by Elisa. [elephant] HCV-HCC26 was performed in the surgical hepatectomy during the first treatment in the hospital. There were 16 males and 10 females. There were 6 cases of well differentiated type, 15 cases of moderately differentiated type and 5 cases of poorly differentiated type. The antibodies in the blood were detected in 10 cases. [methods] the cancer tissue was extracted from the non-cancer tissue and the protein was extracted from the non-cancer tissue. After the protein was extracted, the 2DE was isolated, and the cancer tissue was isolated from the non-cancer tissue. After the cancer tissue was compared with the non-cancer tissue, the protein was isolated from the cancer tissue, and the MALDI-TOF/MS protein was detected. The serum and serum antibodies of the patients with albumin in cancer tissues and cancer tissues showed the presence of autoantibodies. [results] the cancer tissues were compared with the non-cancer tissues, and there were 8 kinds of confirmed genes in the non-cancer tissues, the 11 proteins and the low-protein proteins. In addition, the HSP70family of the same kind of protein is the same as that of the other two proteins. Glutamine synthetase (GS) alpha enolase (ENOA) protein was added to the cancer tissue of the same group. GS "highly differentiated HCC" plus "homogenization". One side of the ENOA low-differentiation HCC communication system has been added to the system, and it has been shown that there is a significant difference between the two groups. HSP70, peroxiredoxin, superoxide dismutase antibody in serum of patients and serum of normal people were detected by Elisa. [results] this time, it is important to think about the process of HCV-HCC cancer, and the antibody in the blood will be cut off in the future. the possibility is very important.