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Published on: May 1, 2020
Phosphorylated 4E-BP1 is associated with tumor progression and adverse prognosis in colorectal cancer
Abstract:
Phosphorylation of eukaryotic translation initiation factor 4E (eIF4E)- binding protein (4E-BP1) results in release of eIF4E, relieving translational repression and enhancing cancerigenic protein synthesis. This study aim to evaluate the level of phosphorylated 4E-BP1 (p-4E-BP1) in colorectal cancer (CRC) and to assess the cor-relation with clinicopathological factors and patient survival. The level of p-4E-BP1 was detected by immunohistochemistry and western bolt in patients with CRC. Then Cox regression model was used to evaluate the prognostic value of all covariates. Among 164 assessed patients, 95 (57.9%) patients showed high level of p-4E-BP1. We noted that the level of p-4E-BP1 was significantly associated with tumor differentiation, invasive depth, lymph node metastasis and TNM stage. Then we compared the mRNA and protein expressions of 4E-BP1 in tumor regions and paired adjacent normal colorectal mucosal tissues in CRC patients. mRNA and protein expressions of 4E-BP1 did not differ between colorectal cancer and corresponding normal tissues, while the phosphorylation level of 4E-BP1 was markedly increased in CRC. Survival analysis and Cox proportional hazards model revealed that p-4E-BP1 was an independent adverse prognostic factor for both overall survival (OS) (HR = 5.414, p = 0.029) and progression-free survival (PFS) (HR = 4.754, p = 0.042). Herein, our results indicate that high p-4E-BP1 level is associated with tumor progression and adverse prognosis. p-4E-BP1 might be a novel biomarker to predict the clinical outcome of patients with CRC.
Insights
High levels of phosphorylated 4E-BP1 (p-4E-BP1) are linked to colorectal cancer progression. This protein may serve as a novel biomarker for predicting patient outcomes and survival in colorectal cancer (CRC).
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Phosphorylation of eukaryotic translation initiation factor 4E (eIF4E)-binding protein (4E-BP1) releases eIF4E, promoting cancer-associated protein synthesis.
- Elevated p-4E-BP1 levels are implicated in various cancers, but its role in colorectal cancer (CRC) requires further elucidation.
Purpose of the Study:
- To evaluate the expression of phosphorylated 4E-BP1 (p-4E-BP1) in colorectal cancer (CRC) tissues.
- To investigate the correlation between p-4E-BP1 levels and clinicopathological factors in CRC patients.
- To assess the prognostic value of p-4E-BP1 for patient survival in CRC.
Main Methods:
- Immunohistochemistry and Western blot were employed to detect p-4E-BP1 levels in 164 CRC patients.
- mRNA and protein expression of 4E-BP1 were compared between tumor and adjacent normal colorectal tissues.
- Cox regression analysis was utilized to determine the prognostic significance of p-4E-BP1.
Main Results:
- A high level of p-4E-BP1 was observed in 57.9% of CRC patients.
- p-4E-BP1 levels significantly correlated with tumor differentiation, invasive depth, lymph node metastasis, and TNM stage.
- While 4E-BP1 mRNA and protein levels did not differ, p-4E-BP1 was markedly increased in CRC tissues.
Conclusions:
- Elevated p-4E-BP1 is associated with tumor progression and adverse prognosis in colorectal cancer.
- p-4E-BP1 serves as an independent adverse prognostic factor for overall survival and progression-free survival in CRC.
- p-4E-BP1 shows potential as a novel biomarker for predicting clinical outcomes in colorectal cancer patients.
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