Mitochondrial Proteomics Approach Reveals Voltage-Dependent Anion Channel 1 (VDAC1) as a Potential Biomarker of Gastric Cancer
Mitochondrial Proteomics Approach Reveals Voltage-Dependent Anion Channel 1 (VDAC1) as a Potential Biomarker of Gastric Cancer
复制标题
线粒体蛋白质组学方法揭示电压依赖性阴离子通道 1 (VDAC1) 作为胃癌的潜在生物标志物。
DOI：
10.1159/000438588
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发表时间：
2015-01-01
影响因子：
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通讯作者：
Wu, Jindao
中科院分区：
文献类型：
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作者：
Gao, Wen;Xu, Jing;Wu, Jindao
背景/目的：胃癌（GC）仍然是世界上第二大癌症相关死亡原因。成功的早期癌症检测受到缺乏高度敏感和特异性生物标志物的阻碍。线粒体功能障碍导致许多癌症的侵袭性致癌表型。我们假设线粒体蛋白质组的变化是支持GC发展所必需的。研究方法：采用TMT法结合质谱分析，定量分析非癌组织和胃癌组织中线粒体蛋白丰度的变化。结果：在包含738个已鉴定蛋白质的总数据集中，约40.1%被发现是线粒体及其相关蛋白质。其中，234个蛋白在胃癌组织中表达上调或下调至少1.5倍。许多标记物（如HSP 70、HSP 60、HSP 90、富含亮氨酸的五肽重复序列（LRPPRC）、SOD 2和组织蛋白酶B）先前被报道为GC的生物标记物。此外，一些潜在的生物标志物参与的线粒体氧化磷酸化和活性脂肪酸氧化，首次发现差异表达的GC样品。我们的研究结果还表明VDAC 1可能是GC的一种新的生物标志物。结论：肿瘤组织亚细胞蛋白质组学研究是可行的，是研究肿瘤发生机制的一条有前途的途径。版权所有（C）2015 S. Karger AG，巴塞尔
Background/Aims: Gastric cancer (GC) remains the second leading cause of cancer-related deaths in the world. Successful early cancer detection is hampered by lack of highly sensitive and specific biomarkers. Mitochondrial dysfunction contributes to an aggressive carcinogenic phenotype of many cancers. We hypothesized that changes in the mitochondrial proteome are required to support development of GC. Methods: TMT method followed by mass spectrometry analysis was utilized to quantify alterations in protein abundance in mitochondria enriched between noncancer and gastric cancer tissues. Results: Of a total data set that included 738 identified proteins, about 40.1% were found to be mitochondrial and associated proteins. Among them, 234 proteins were at least 1.5-fold up- or down-regulated in the gastric cancer compared with the adherent normal tissues. A number of markers (e.g. HSP70, HSP60, HSP90, leucine-rich pentatricopeptide repeat containing (LRPPRC), SOD2 and cathepsin B) were previously reported as biomarkers of GC. Additionally, several potential biomarkers participated in mitochondrial oxidative phosphorylation and active fatty acid oxidation were firstly identified differentially expressed in GC samples. Our findings also suggest that VDAC1 may be a novel biomarker for GC. Conclusion: The results show that subcellular proteomics of tumor tissue is feasible and a promising avenue for exploring oncogenesis. Copyright (C) 2015 S. Karger AG, Basel