<p>4E-BP1^Thr46 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</p>

Abstract

These authors contributed equally to this work 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 noncancerous 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.

Overexpression of p-4EBP1 associates with p-eIF4E and predicts poor prognosis for non-small cell lung cancer patients with resection

“…Taking together, these data suggest high expressed p-eIF4E and p-4EBP1 could be new prognostic marker for NSCLC. Several research pointed out that overexpression of p-4EBP1 has been found in a range of other tumors, including ovarian cancer, hepatocellular carcinoma, and breast cancer, which confirmed their important role in various cancers [ 14 , 22 , 23 ]. In addition, 4EBP1 is associated with prognosis of patients in several kinds of cancers, such as renal cell cancer and small cell lung cancer [ 15 , 16 ].…”

Diagnostic and Prognostic Value of Protein Post-Translational Modifications in Hepatocellular Carcinoma

“…HCC with early formation of portal vein tumor thrombosis (PVTT) had a higher risk of metastasis. Lin et al 67 performed a phosphorylated proteomic analysis and identified a total of 1,745 phosphoproteins in HCC tissues, normal tissues, and PVTT tissues. The results showed that HCC and PVTT tissues had higher phosphorylation levels of 4E-BP1 than surrounding noncancerous tissues.…”

Potential Biomarkers for Liver Cancer Diagnosis Based on Multi-Omics Strategy

“…Aberrant protein phosphorylation is associated with HCC ( 142 ) and more phosphorylation alterations have been elucidated with the development of omics methods. Elevating phosphorylation levels of 4E-binding protein 1 (4E-BP1) on Thr46 could be used to predict the early recurrence and metastasis of HCC ( 68 ). The level of Ser36 phosphorylation of aldolase A (ALDOA) was increased and could be used as a potential biomarker for HCC ( 71 ).…”