ANXA2(TYr23) and FLNA(Ser2152) phosphorylation associate with poor prognosis in hepatic carcinoma revealed by quantitative phosphoproteomics analysis
ANXA2(TYr23) and FLNA(Ser2152) phosphorylation associate with poor prognosis in hepatic carcinoma revealed by quantitative phosphoproteomics analysis
复制标题
定量磷酸蛋白质组学分析显示 ANXA2(Tyr23) 和 FLNA(Ser2152) 磷酸化与肝癌预后不良相关。
DOI：
10.1016/j.jprot.2019.03.017
复制
发表时间：
2019
影响因子：
3.3
通讯作者：
Huang Aimin
中科院分区：
文献类型：
--
作者：
Xing Xiaohua;Yuan Hui;Sun Ying;Ke Kun;Dong Xiuqing;Chen Hui;Liu Xiaolong;Zhao Bixing;Huang Aimin
肝癌是最常见的恶性肿瘤之一，多数患者预后极差。早期预测和干预肝癌复发/转移是改善患者临床预后的最有效途径。在这里，我们使用等压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来鉴定与肝癌复发/转移相关的生物标志物，这些标志物在转移能力增强的肝癌细胞系中。共有60个磷酸化蛋白对应的75个磷酸化肽发生了显著的异常，这些磷酸化蛋白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，在高转移细胞中，在肿瘤转移过程中起关键作用的关键信号通路明显过度激活。此外，与低转移细胞相比，flnaser2152和anxa2tyr23的磷酸化在高转移细胞中明显上调。通过在大规模临床样本中进一步研究flnaser2152和anxa2tyr23磷酸化的临床意义，发现flnaser2152和anxa2tyr23过磷酸化与预后不良相关，可能是原发性肝癌潜在的预后生物标志物。当flnaser2152联合ANXA2Tyr23时，对OS和TTR都有更好的预后价值。
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 FLNASer2152and ANXA2Tyr23were 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 FLNASer2152and ANXA2Tyr23in large-scale clinical samples, revealed that the over phosphorylation of FLNASer2152and ANXA2Tyr23were associated with poor prognosis and might be potential prognostic biomarkers for the primary hepatoma. When FLNASer2152combined with ANXA2Tyr23, it had a better prognostic value for both OS and TTR.