4E-BP1Thr46 Phosphorylation Association with Poor Prognosis in Quantitative Phosphoproteomics of Portal Vein Tumor Thrombus Revealed that 4E-BP1Thr46 Phosphorylation is Associated with Poor Prognosis in HCC
4E-BP1Thr46 Phosphorylation Association with Poor Prognosis in Quantitative Phosphoproteomics of Portal Vein Tumor Thrombus Revealed that 4E-BP1Thr46 Phosphorylation is Associated with Poor Prognosis in HCC
复制标题
门静脉肿瘤血栓定量磷酸化蛋白质组学中 4E-BP1(Thr46) 磷酸化与不良预后相关性揭示 4E-BP1(Thr46) 磷酸化与 HCC 不良预后相关
DOI：
10.2147/cmar.s230849
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发表时间：
2020-01-01
影响因子：
3.3
通讯作者：
Liu, Jingfeng
中科院分区：
文献类型：
--
作者：
Lin, Xincong;Huang, Yao;Liu, Jingfeng
目的：门静脉癌栓（PVTT）的早期形成是肝细胞癌（HCC）转移的重要特征，但迄今为止，肝癌转移中PVTT的病因尚不清楚。我们的目的是找到高度敏感和特异性的生物标志物，用于预测HCC预后Patients and methods：我们使用同量异位素标签相对和绝对定量（iTRAQ）为基础的定量磷酸化蛋白质组学方法，以调查原发性HCC组织，周围的非癌组织和PVTT组织中的HCC与PVTT的分子特征。不同的蛋白质组谱在三组进行了调查，并可能揭示不同的潜在的分子mechanism.Results：在总共，我们确定了1745磷蛋白与2724磷酸肽和4594磷酸化位点在三组。在这些磷蛋白中，PVTT/Pan组中有80种磷蛋白表达异常，HCC/Pan组中有51种磷蛋白表达异常，PVTT/HCC组中有10种磷蛋白表达异常。此外，4 E-BP 1的磷酸化水平在HCC组织和PVTT组织中与周围非癌组织相比升高，并且磷酸化水平的升高倍数变化高于4 E-BP 1的表达水平。结论：4 E-BP 1（Thr 46）的高磷酸化水平可作为HCC早期复发转移的生物标志物。
Purpose: Early formation of portal vein tumor thrombosis (PVTT) is a key characteristic of hepatocellular carcinoma (HCC) metastasis, but to date, the aetiology of PVTT in HCC metastasis is largely unknown. We aim to find highly sensitive and specific biomarkers for the prediction of HCC prognosis.Patients and methods: We used isobaric tags for relative and absolute quantitation (iTRAQ) based quantitative phosphoproteomics approach to investigate the molecular signatures of the HCC with PVTT in primary HCC tissues, surrounding non-cancerous tissues and PVTT tissues. The different proteome profiles in three groups were investigated and might reveal different underlying molecular mechanisms.Results: In total, we identified 1745 phosphoproteins with 2724 phosphopeptides and 4594 phosphorylation sites in three groups. Among these phosphoproteins, 80 phosphoproteins were dysregulated in PVTT/Pan group, 51 phosphoproteins were dysregulated in HCC/Pan group, and 10 phosphoproteins were dysregulated in PVTT/HCC group. Furthermore, the phosphorylation of 4E-BP1 was elevated in HCC tissues and PVTT tissues in comparison with surrounding non-cancerous tissues, and the elevated fold change of phosphorylation level was higher than that in expression level of 4E-BP1. The further IHC analysis in acohort of 20 HCC tissues showed that the phosphorylation of 4E-BP1 on Thr46 might be closely related to HCC prognosis.Conclusion: The high phosphorylation level of 4E-BP1(Thr46) might serve as a biomarker for the diagnosis of early recurrence and metastasis of HCC.