ANXA2TYr23 and FLNASer2152 phosphorylation associate with poor prognosis in hepatic carcinoma revealed by quantitative phosphoproteomics analysis

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(Ser2152) and ANXA2(TYr23) 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(Ser2152) and ANXA2(TYr23) in largescale clinical samples, revealed that the over phosphorylation of FLNA(Ser2152) and ANXA2(TYr23) were associated with poor prognosis and might be potential prognostic biomarkers for the primary hepatoma. When FLNA(Ser2152) combined with ANXA2(TYr23) , it had a better prognostic value for both OS and TTR.