Proteomic Analysis of Hepatocellular Carcinoma Tissues With Encapsulation Shows Up-regulation of Leucine Aminopeptidase 3 and Phosphoenolpyruvate Carboxykinase 2

Proteomic Analysis of Hepatocellular Carcinoma Tissues With Encapsulation Shows Up-regulation of Leucine Aminopeptidase 3 and Phosphoenolpyruvate Carboxykinase 2
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DOI:
10.21873/cgp.20261
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发表时间:
2021-05-01
影响因子:
2.5
通讯作者:
Kuramitsu, Yasuhiro
Kuramitsu, Yasuhiro
中科院分区:
医学4区
文献类型:
--
作者:
Kuhara, Keisuke;Kitagawa, Takao;Kuramitsu, Yasuhiro

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背景/目的:肿瘤是世界范围内最致命的疾病,其最致命的特征是侵袭和转移。肝细胞癌(HCC)是世界范围内最致命的癌症之一。HCC常表现为包膜,与预后较好有关。在这项研究中,蛋白质组学分析的肝癌组织有和无包膜,以阐明在包膜中发挥重要作用的因素。材料与方法:从接受手术肝切除术的诊断为HCC的患者中获得被包膜包围的五个HCC组织和打破包膜的五个HCC组织。采用双向凝胶电泳(2-DE)技术分离蛋白质样品,通过凝胶成像分析软件鉴定包膜与非包膜HCC组织中表达差异的蛋白质点。采用液相色谱-串联质谱(LC-MS/MS)对筛选出的蛋白质点进行分析鉴定。结果:双向电泳结果显示有包膜和无包膜肝癌组织中有14个蛋白质表达差异点。其中,9个在无包膜的HCC组织中上调,5个下调。Western blot验证证实,亮氨酸氨基肽酶3(LAP 3)和磷酸烯醇式丙酮酸羧激酶线粒体(PCK 2)在有包膜的HCC组织中显著上调,与包膜破裂的HCC组织相比。结论:LAP 3和PCK 2可能是维持肝癌组织包膜的重要因素。
Background/Aim: Cancer is the most fatal disease worldwide whose most lethal characteristics are invasion and metastasis. Hepatocellular carcinoma (HCC) is one of the most fatal cancers worldwide. HCC often shows encapsulation, which is related to better prognosis. In this study, proteomic analysis of HCC tissues with and without encapsulation was performed, in order to elucidate the factors which play important roles in encapsulation. Materials and Methods: Five HCC tissues surrounded by a capsule and five HCC tissues which broke the capsule were obtained from patients diagnosed with HCC who underwent surgical liver resection. Protein samples from these tissues were separated by two-dimensional gel electrophoresis (2-DE), and the protein spots whose expression was different between encapsulated and non-encapsulated HCC tissues were identified through gel imaging analysis software. The selected protein spots were analyzed and identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Two-DE analysis showed 14 spots whose expression was different between encapsulated and non-encapsulated HCC tissues. Of these, 9 were up-regulated and 5 were down-regulated in HCC tissues without encapsulation. The validation by Western blot confirmed that leucine aminopeptidase 3 (LAP3) and phosphoenolpyruvate carboxykinase mitochondrial (PCK2) were up-regulated significantly in HCC tissues with a capsule, compared to HCC tissues that broke the capsule. Conclusion: These findings suggest that LAP3 and PCK2 could be factors responsible for the maintenance of encapsulation in HCC tissues.