title: Elevated serum insulin-like growth factor (IGF)-II and IGF binding protein-2 in patients with colorectal cancer.
abstract: This study explored the relationships of serum insulin-like growth factors, IGF-I and IGF-II, and their binding proteins (IGFBP)-2 and IGFBP-3, with key clinicopathological parameters in 92 patients with colorectal cancer (cases). Comparisons were made with 57 individuals who had a normal colonoscopy (controls). Serial changes were examined in 27 cases. As IGF-related peptides are age- and sex-dependent, absolute concentrations were converted to standard deviation scores (SDS). Mean IGF-II SDS were elevated in Dukes A (n = 12, P< 0.001) and Dukes B (n = 25, P< 0.001) cases compared with controls, but not in advanced disease. Compared with controls, mean IGFBP-2 SDS were significantly elevated in patients with Dukes B (P< 0.001), Dukes C (n = 13, P< 0.001) and advanced disease (n = 42, P< 0.0001), with a significant trend from early to advanced disease (one-way ANOVA, P< 0.001). Furthermore, IGFBP-2 SDS were positively related to tumour size (P = 0.01) and fell significantly in patients following curative resection (P = 0.04), suggesting that circulating levels reflect tumour load. We tested the potential tumour marker characteristics of IGFBP-2 SDS against three endpoints: metastasis alone; local pelvic recurrence alone; and metastasis and recurrence combined. The sensitivities for IGFBP-2 alone (>/= + 2SD) were modest at 55%, 46%, and 52%, but in combination with CEA, increased substantially to 90%, 77% and 86%, respectively. We conclude that the serum IGF-II and IGFBP-2 profiles may provide insights into underlying biological mechanisms, and that serum IGFBP-2 may have an adjunct role in cancer surveillance in patients with colorectal cancer.
authors.affiliation: Department of Surgery, Christie Hospital NHS Trust, Manchester, M20 4BX.
authors.forename: A G
authors.initials: AG
authors.lastname: Renehan
authors.forename: J
authors.initials: J
authors.lastname: Jones
authors.forename: C S
authors.initials: CS
authors.lastname: Potten
authors.forename: S M
authors.initials: SM
authors.lastname: Shalet
authors.forename: S T
authors.initials: ST
authors.lastname: O'Dwyer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000032:analysis*; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis*; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007335:Insulin-Like Growth Factor II / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D012680:Sensitivity and Specificity
chemical_list: D014408:Biomarkers, Tumor; D018971:Insulin-Like Growth Factor Binding Protein 2; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II