Advanced Research Promotion Centre, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan.
Division of Oral and Maxillofacial Surgery, Department of Human Biology and Pathophysiology, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu, Japan.
Cancer Genomics Proteomics. 2021 May-Jun;18(3):307-316. doi: 10.21873/cgp.20261.
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.
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).
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.
These findings suggest that LAP3 and PCK2 could be factors responsible for the maintenance of encapsulation in HCC tissues.
背景/目的：癌症是全球最致命的疾病，其最致命的特征是侵袭和转移。肝细胞癌（HCC）是全球最致命的癌症之一。HCC 通常表现出包膜，这与更好的预后有关。在这项研究中，对有包膜和无包膜的 HCC 组织进行了蛋白质组学分析，以阐明在包膜形成中起重要作用的因素。
从接受手术肝切除的 HCC 患者中获得了 5 个被包膜包围的 HCC 组织和 5 个突破包膜的 HCC 组织。这些组织的蛋白质样品通过二维凝胶电泳（2-DE）分离，通过凝胶成像分析软件识别包膜和非包膜 HCC 组织之间表达差异的蛋白质斑点。通过液相色谱-串联质谱（LC-MS/MS）对选定的蛋白质斑点进行分析和鉴定。
2-DE 分析显示，包膜和非包膜 HCC 组织之间有 14 个表达差异的蛋白质斑点。其中，无包膜 HCC 组织中 9 个上调，5 个下调。Western blot 验证证实，与突破包膜的 HCC 组织相比，包膜内 HCC 组织中亮氨酸氨肽酶 3（LAP3）和磷酸烯醇丙酮酸羧激酶线粒体（PCK2）显著上调。
这些发现表明 LAP3 和 PCK2 可能是维持 HCC 组织包膜的因素。
