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.

Keywords: Immunohistochemistry; Prognosis; Small-cell lung cancer; p-4E-BP1.