title: Overexpression of phosphorylated 4E-binding protein 1 and its clinicopathological significances in gastric cancer.
abstract: Multiple intracellular transforming signals regulate eukaryotic translation initiation factor 4E (eIF4E)-binding protein (4E-BP1). The signals result in hierarchical phosphorylation of 4E-BP1, resulting in release of eIF4E, relieving translational repression and enhancing oncogenic protein synthesis. This study assessed the expression of phosphorylated 4E-BP1 (p-4E-BP1) in gastric cancer and its correlation with clinicopathological parameters and patient survival. Tissue microarray blocks were generated from 179 gastric carcinomas and immunohistochemically stained for p-4E-BP1. The expression of p-4E-BP1 was higher in tumors that were intestinal-type (P=0.028); had a diameter smaller than 5cm (P=0.001); were lower pathological T stage (P<0.001), N stage (P=0.004), or TNM stage (P<0.001); did not have distant metastasis (P=0.027). High p-4E-BP1 expression significantly correlated with prolonged overall survival (P=0.046) and disease-free survival (P=0.035), but was not an independent prognostic factor in multivariate analysis. Our results indicate that p-4E-BP1 is more highly expressed in early gastric cancers than in advanced ones, and has limited potential as an independent prognostic biomarker in patients with gastric cancer. Larger well-controlled studies with molecular validation are warranted to elucidate more exact prognostic significance and working mechanism of p-4E-BP1 in gastric cancer.
authors: Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea.
authors: Hyoun Wook
authors: HW
authors: Lee
authors: Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea.
authors: Moon-Il
authors: MI
authors: Park
authors: Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea.
authors: Mee-Seon
authors: MS
authors: Kim
authors: Department of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea.
authors: Seok-Hyun
authors: SH
authors: Kim
authors: Department of Pathology, Dong-A University College of Medicine, Busan, South Korea.
authors: Mee Sook
authors: MS
authors: Roh
authors: Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors: Kyungeun
authors: K
authors: Kim
authors: Department of Clinical Laboratory Science, Gimhae College, Gimhae, South Korea.
authors: Sang Bong
authors: SB
authors: Jung
authors: Department of Pathology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, South Korea. Electronic address: eunhee27.lee@samsung.com.
authors: Eun Hee
authors: EH
authors: Lee
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D046888:Tissue Array Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins
keywords: Gastric cancer; Immunohistochemistry; Prognosis; p-4E-BP1