Phosphorylated 4E-BP1 is associated with tumor progression and adverse prognosis in colorectal cancer

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 correlation 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.