Elevated serum antibodies against insulin-like growth factor-binding protein-2 allow detecting early-stage cancers: evidences from glioma and colorectal carcinoma studies

Ann Oncol. 2012 Sep;23(9):2415-2422. doi: 10.1093/annonc/mds007. Epub 2012 Feb 22.

Abstract

Background: Tumor-specific immunity of insulin-like growth factor-binding protein-2 (IGFBP-2) has been reported in several cancers. We aimed to assess the role of serum IGFBP-2 antibodies (IGFBP-2 Abs) in early cancer detection.

Patients and methods: Glioma and colorectal carcinoma (CRC) were used as models. Serum IGFBP-2 and IGFBP-2 Abs were measured in 260 tumor patients (145 gliomas, 45 colorectal polyps, and 70 CRCs) and 141 controls. Receiver operating characteristic curves were applied.

Results: Serum IGFBP-2 Ab levels were significantly elevated in tumors (mean: 82 ng/ml, median: 17 ng/ml, range: 0-1387 ng/ml) compared with controls (11, 0, 0-212 ng/ml) (P < 0.0001) and higher in early than advanced cancers opposite of serum IGFBP-2 levels. IGFBP-2 Abs effectively discriminated between controls and grade II and III gliomas [area under the curve (AUC): 0.821-0.864; 95% confidence interval (CI) = 0.762-0.936; P < 0.0001], and CRC I-II (AUC: 0.668; 95% CI = 0.566-0.770; P = 0.002) as well as indicative of advanced polyps at high risk of CRC (AUC: 0.72; 95% CI = 0.630-0.811; P < 0.0001). The sensitivity and specificity for diagnosing grade II-III gliomas reached 66%-84% and 81%. Combined serum IGFBP-2 and IGFBP-2 Abs augmented the discriminative power of all stage tumors (AUC: 0.823), gliomas (AUC: 0.800), and CRCs (AUC = 0.917).

Conclusion: Our results first demonstrate IGFBP-2 Abs for early cancer detection and in combination of serum IGFBP-2 for improved cancer diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Astrocytoma / blood*
  • Astrocytoma / diagnosis
  • Astrocytoma / metabolism
  • Autoantibodies / blood*
  • Carcinoma / blood*
  • Carcinoma / diagnosis
  • Carcinoma / metabolism
  • Case-Control Studies
  • Central Nervous System Neoplasms / blood*
  • Central Nervous System Neoplasms / diagnosis
  • Central Nervous System Neoplasms / metabolism
  • Colorectal Neoplasms / blood*
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / metabolism
  • Early Detection of Cancer
  • Female
  • Humans
  • Insulin-Like Growth Factor Binding Protein 2 / blood
  • Insulin-Like Growth Factor Binding Protein 2 / immunology*
  • Male
  • Middle Aged
  • Prospective Studies
  • ROC Curve
  • Statistics, Nonparametric
  • Young Adult

Substances

  • Autoantibodies
  • Insulin-Like Growth Factor Binding Protein 2