IGFBP-3 and IGFBP-10 (CYR61) up-regulation during the development of Barrett's oesophagus and associated oesophageal adenocarcinoma: potential biomarkers of disease risk.
Dys-regulation of the insulin-like growth factor (IGF) system increases the risk of a number of malignancies. The aim of this study was to investigate the role of members of the IGF binding protein (IGFBP) superfamily in the development of oesophageal adenocarcinoma (EAC) and their possible use as markers of disease risk. Expression of IGFBP-2, IGFBP-3, IGFBP-4, and IGFBP-10/CYR61 was assessed using Real-Time-polymerase chain reaction (PCR) and immunohistochemistry in oesophageal tissues from Barrett's oesophagus (BE) patients with and without associated EAC, and in control subjects. IGFBP-3, IGFBP-4, and IGFBP-10/CYR61 mRNA levels were up-regulated in Barrett's (n=17) and tumour tissue of EAC patients (n=18) compared with normal tissue of control subjects without BE or EAC (n=18) (p<0.001). Over-expression of IGFBP-3 and IGFBP-10/CYR61 proteins was observed in Barrett's, dysplastic and tumour tissue of EAC cases (n=47 for IGFBP-10; n=39 for IGFBP-3) compared with adjacent normal epithelium (p<0.050). Notably, IGFBP-3, IGFBP-4, and IGFBP-10/CYR61 expression in Barrett's tissue of EAC cases (n=17) was significantly (p<0.001) higher than in Barrett's tissue of BE patients with no sign of progression to cancer (n=15). Overall, the results suggest that members of the IGFBP superfamily are up-regulated during oesophageal carcinogenesis and merit further investigation as markers of EAC risk.
Di Martino
E
E
Molecular Epidemiology Unit, Centre for Epidemiology and Biostatistics, Leeds Institute for Genetics, Health and Therapeutics, University of Leeds, Leeds, UK.
Wild
C P
CP
Rotimi
O
O
Darnton
J S
JS
Olliver
R J
RJ
Hardie
L J
LJ
D000230:Adenocarcinoma; D000328:Adult; D000368:Aged; D001471:Barrett Esophagus / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D015415:Biomarkers / Q000032:analysis; D016022:Case-Control Studies; D055515:Cysteine-Rich Protein 61; D004938:Esophageal Neoplasms / Q000175:diagnosis* / Q000209:etiology / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017874:Immediate-Early Proteins; D007150:Immunohistochemistry; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis* / Q000235:genetics; D018969:Insulin-Like Growth Factor Binding Proteins / Q000032:analysis* / Q000235:genetics; D036341:Intercellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D015854:Up-Regulation / Q000235:genetics
D015415:Biomarkers; C501848:CCN1 protein, human; D055515:Cysteine-Rich Protein 61; D017874:Immediate-Early Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger