The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The School of Basic Medical Sciences, Fujian Medical University, Fuzhou 350004, People's Republic of China.
The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou 350025, People's Republic of China; The First Affiliated Hospital of Fujian Medical University, Fuzhou 350007, People's Republic of China.
J Proteomics. 2019 May 30;200:111-122. doi: 10.1016/j.jprot.2019.03.017. Epub 2019 Apr 2.
Hepatoma is one of the most common malignant tumors, and most patients have very poor prognosis. Early prediction and intervention of the hepatoma recurrence/metastasis are the most effective way to improve the patients' clinical outcomes. Here, we used isobaric tags for relative and absolute quantitation (iTRAQ) based quantitative phospho-proteomics approach to identify biomarkers associated with hepatoma recurrence/metastasis in hepatoma cell lines with increasing metastasis ability. In total, 75 phosphorylated peptides corresponding to 60 phosphoproteins were significantly dysregulated and the participated biological processes of these phosphoproteins were tightly associated with tumor metastasis. Further signaling pathway analysis revealed that key signaling pathways which play crucial roles in cancer metastasis have been significantly over activated in the highly metastatic cells. Furthermore, the phosphorylation of FLNA and ANXA2 were validated to be significantly up regulated in the high-metastatic cells comparing with the low-metastatic cells. By further investigation the clinical significance of the phosphorylation of FLNA and ANXA2 in large-scale clinical samples, revealed that the over phosphorylation of FLNA and ANXA2 were associated with poor prognosis and might be potential prognostic biomarkers for the primary hepatoma. When FLNA combined with ANXA2, it had a better prognostic value for both OS and TTR.
肝癌是最常见的恶性肿瘤之一，大多数患者预后极差。早期预测和干预肝癌的复发/转移是改善患者临床结局的最有效方法。在这里，我们使用同位素标记相对和绝对定量（iTRAQ）基于定量磷酸化蛋白质组学方法来鉴定与肝癌细胞系中具有增加转移能力的肝癌复发/转移相关的生物标志物。总共鉴定到 75 个磷酸化肽，对应 60 个磷酸化蛋白，这些磷酸化蛋白的参与的生物学过程与肿瘤转移密切相关。进一步的信号通路分析表明，在高转移性细胞中，关键的信号通路在癌症转移中起着至关重要的作用，这些信号通路被显著过度激活。此外，与低转移性细胞相比，FLNA 和 ANXA2 的磷酸化在高转移性细胞中被证实显著上调。通过进一步研究 FLNA 和 ANXA2 的磷酸化在大规模临床样本中的临床意义，表明 FLNA 和 ANXA2 的过度磷酸化与预后不良相关，可能是原发性肝癌的潜在预后生物标志物。当 FLNA 与 ANXA2 联合时，对 OS 和 TTR 都有更好的预后价值。
