IGF-Binding Proteins, Adiponectin, and Survival in Metastatic Colorectal Cancer: Results from CALGB (Alliance)/SWOG 80405

Brendan J. Guercio, Sui Zhang, Fang Shu Ou, Alan P. Venook, Donna Niedzwiecki, Heinz Josef Lenz, Federico Innocenti, Michael N. Pollak, Andrew B. Nixon, Brian C. Mullen, Bert H. O'Neil, James E. Shaw, Blase N. Polite, Benson Al Bowen, James N. Atkins, Richard M. Goldberg, Justin C. Brown, Eileen M. O'Reilly, Robert J. Mayer, Charles D. BlankeCharles S. Fuchs, Jeffrey A. Meyerhardt

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Energy balance-related biomarkers are associated with risk and prognosis of various malignancies. Their relationship to survival in metastatic colorectal cancer (mCRC) requires further study. Methods: Baseline plasma insulin-like growth factor (IGF)-1, IGF-binding protein (IGFBP)-3, IGFBP-7, C-peptide, and adiponectin were measured at time of trial registration in a prospective cohort of patients with mCRC participating in a National Cancer Institute-sponsored trial of first-line systemic therapy. We used Cox proportional hazards regression to adjust for confounders and examine associations of each biomarker with overall survival (OS) and progression-free survival (PFS). P values are 2-sided. Results: Median follow-up for 1086 patients was 6.2 years. Compared with patients in the lowest IGFBP-3 quintile, patients in the highest IGFBP-3 quintile experienced an adjusted hazard ratio (HR) for OS of 0.57 (95% confidence interval [CI] = 0.42 to 0.78; Pnonlinearity < .001) and for PFS of 0.61 (95% CI = 0.45 to 0.82; Ptrend = .003). Compared with patients in the lowest IGFBP-7 quintile, patients in the highest IGFBP-7 quintile experienced an adjusted hazard ratio for OS of 1.60 (95% CI = 1.30 to 1.97; Ptrend < .001) and for PFS of 1.38 (95% CI = 1.13 to 1.69; Ptrend < .001). Plasma C-peptide and IGF-1 were not associated with patient outcomes. Adiponectin was not associated with OS; there was a nonlinear U-shaped association between adiponectin and PFS (Pnonlinearity = .03). Conclusions: Among patients with mCRC, high plasma IGFBP-3 and low IGFBP-7 were associated with longer OS and PFS. Extreme levels of adiponectin were associated with shorter PFS. These findings suggest potential avenues for prognostic and therapeutic innovation.

Original languageEnglish (US)
Article numberpkaa074
JournalJNCI Cancer Spectrum
Volume5
Issue number1
DOIs
StatePublished - 2021

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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