Plasma insulin-like growth factor-binding protein-2 levels as diagnostic and prognostic biomarker of colorectal cancer.
BACKGROUND
Overexpression of IGF-II and IGF-binding protein (IGFBP)-2 has been reported in several cancers.


OBJECTIVE
We aimed to assess the roles of plasma IGF-II and IGFBP-2 levels as diagnostic and prognostic biomarkers and the impact of loss of imprinting (LOI) of IGF-II on the survival of colorectal cancer (CRC).


METHODS
We conducted a case control and prospective cohort study for diagnostic and prognostic values, respectively.


METHODS
Plasma levels of IGF-II and IGFBP-2 were measured in 162 patients with CRC before surgery, in paired 15 patients after curative surgery, in 24 patients with advanced colon polyps, and in 114 healthy controls between 2003 and 2006 in National Taiwan University Hospital.


RESULTS
The area under the curve values of using IGFBP-2 as a diagnostic marker for advanced colon polyp and CRC were 0.654 [95% confidence interval (CI) = 0.547-0.76; P = 0.017] and 0.815 (95% CI = 0.766-0.864; P < 0.001), respectively. The sensitivity and specificity for diagnosing CRC were 80.2 and 64%, respectively, if the cutoff value of IGFBP-2 was 377 ng/ml. In the multivariate Cox proportional hazards regression model, higher IGFBP-2 levels were associated with increased risk of mortality [hazard ratio (HR) = 2.46; P = 0.017], whereas higher IGF-II levels were associated with reduced risk of mortality (HR = 0.42; P = 0.044). LOI of IGF-II was associated with increased risk of mortality (HR = 7.91; P = 0.014) in patients with stage IV disease.


CONCLUSIONS
IGFBP-2 is a potential diagnostic and prognostic biomarker of CRC. LOI of IGF-II is significantly associated with poor prognosis in patients with stage IV disease.
Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, College of Medicine, No. 7, Chung-Shan S. Road, Taipei 100, Taiwan.
Jyh-Ming
JM
Liou
Chia-Tung
CT
Shun
Jin-Tung
JT
Liang
Han-Mo
HM
Chiu
Mei-Jyh
MJ
Chen
Chien-Chuan
CC
Chen
Hsiu-Po
HP
Wang
Ming-Shiang
MS
Wu
Jaw-Town
JT
Lin
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D003111:Colonic Polyps / Q000175:diagnosis / Q000601:surgery; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000601:surgery; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D018450:Disease Progression; D005260:Female; D018392:Genomic Imprinting; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000097:blood; D007335:Insulin-Like Growth Factor II / Q000032:analysis / Q000378:metabolism*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D018971:Insulin-Like Growth Factor Binding Protein 2; D012313:RNA; D007335:Insulin-Like Growth Factor II; D004247:DNA