title: Prognostic significance of phosphorylated 4E-binding protein 1 in non-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 non-small cell lung cancer (NSCLC) and its correlation with clinicopathological parameters and patient survival. In addition, we investigated whether phosphorylation site made a difference in outcome. Tissue microarray blocks were generated from 73 NSCLC samples and immunohistochemically stained for p-4E-BP1 Thr37/46 and p-4E-BP1 Thr70. Both p-4E-BP1 Thr37/46 and p-4E-BP1 Thr70 were more highly expressed in squamous cell carcinoma than in adenocarcinoma (P = 0.006 and P = 0.003, respectively). Expression of p-4E-BP1 Thr70 was higher in tumours with a diameter larger than 3 cm (P = 0.024) and nodal metastasis (P = 0.053). High p-4E-BP1 Thr70 expression significantly correlated with worse overall survival (P = 0.001) and was an independent prognostic factor (hazard ratio 2.64, P = 0.004). p-4E-BP1 Thr37/46 had no prognostic significance. Phosphorylation site affected the prognostic significance of p-4E-BP1. p-4E-BP1 Thr70 is a candidate biomarker to predict poor prognosis in patients with NSCLC.
authors.affiliation: Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Hyoun Wook
authors.initials: HW
authors.lastname: Lee
authors.affiliation: Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Lee
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Ji Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Jeong-Eun
authors.initials: JE
authors.lastname: Kim
authors.affiliation: Division of Hematology and Medical Oncology, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Seok-Hyun
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Radiation Oncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Tae Gyu
authors.initials: TG
authors.lastname: Kim
authors.affiliation: Department of Cardiovascular and Thoracic Surgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Sang Won
authors.initials: SW
authors.lastname: Hwang
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine Changwon, South Korea.
authors.forename: Kyung Woo
authors.initials: KW
authors.lastname: Kang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018797:Cell Cycle Proteins; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D015996:Survival Rate
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins
keywords: Non-small cell lung cancer; immunohistochemistry; p-4E-BP1; prognosis