Phosphorylated 4E-binding protein 1 expression is associated with poor prognosis in small-cell lung cancer

Abstract

Phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) binding protein (4E-BP1) results in release of eIF4E, which sequentially relieves translational repression and enhances oncogenic protein synthesis. We assessed the expression of phosphorylated 4E-BP1 (p-4E-BP1) in small-cell lung cancer (SCLC) and its correlation with clinicopathological factors and patient survival. This study included 117 SCLCs, which comprised 108 primary and 9 metastatic tumor tissues. We performed immunohistochemical staining for p-4E-BP1 in 117 tumors and found that 77 (66 %) were positive for p-4E-BP1 with cytoplasmic and/or nuclear immunostaining. The positive rate of p-4E-BP1 staining was significantly higher in never smokers (p = 0.034) and metastatic tumor tissues (p = 0.027). Patients with p-4E-BP1-positive SCLC tended to have poor performance status, although the difference was not statistically significant (p = 0.087). High p-4E-BP1 expression was significantly correlated with worse overall survival (OS) in all cohorts (p = 0.016). After stratification by clinical stage, p-4E-BP1 expression showed a stronger relationship with OS in patients with limited disease (p = 0.008). In addition, when stratified by treatment status, p-4E-BP1 expression was still significantly associated with worse OS in a subgroup of patients who completed treatment (p = 0.021). Our results indicate that p-4E-BP1 expression could represent oncogenic potential and contribute to the progression and aggressiveness of SCLC, suggesting it could be a candidate prognostic biomarker of SCLC, especially in limited disease.

peIF4E as an independent prognostic factor and a potential therapeutic target in diffuse infiltrating astrocytomas

“…We showed that the levels of these factors (p4E‐BP1, peIF4E) increase during tumor progression and that peIF4E, age, and histologic grade were independent prognostic factors in the multivariate analysis. These results are consistent with those of previous studies in several types of carcinomas, where p4E‐BP1, eIF4E, and peIF4E were overexpressed, associated with a poorer prognosis, and considered critical “funnel factors” in cell signaling .…”

Scutellarin suppresses proliferation and promotes apoptosis in A549 lung adenocarcinoma cells via AKT/mTOR/4EBP1 and STAT3 pathways

“…4E‐BP1 is a negative regulator of protein translation in mammalian cells and can be inactivated by p‐mTOR, which promotes its dissociation from eIF‐4E. Dephosphorylated 4EBP1 combines with eIF‐4E and inhibits the initiation of translation in the presence of mTOR inhibitors . Our results show that SCU suppresses pan‐AKT, mTOR, and p‐mTOR, and increases 4EBP1 significantly, indicating that the anticancer effects of SCU might be linked to inactivation of the AKT/mTOR/4EBP1 pathway.…”

TRIM59 is a novel potential prognostic biomarker in patients with non-small cell lung cancer: A research based on bioinformatics analysis

“…EIF4EBP1, a critical regulator of MTOR downstream signaling, may be associated with drug resistance in human tumors (70). Phosphorylation of EIF4EBP1 results in release of EIF4E, which enhances the oncogenic protein synthesis and correlates with the poor prognosis in lung cancer (71,72). …”