Journal
JNCI CANCER SPECTRUM
Volume 5, Issue 1, Pages -Publisher
OXFORD UNIV PRESS
DOI: 10.1093/jncics/pkaa074
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Funding
- National Cancer Institute of the National Institutes of Health [U10CA180821, U10CA180882, U10CA180857, U10CA180790, U10CA180791, U10CA180795, U10CA180826, U10CA180836, U10CA180838, U10CA180867, UG1CA189858, U10CA180820, U10CA180888, U10CA180830, R01 CA169141, R01 CA118553, R01CA149222, R00CA218603, R25CA203650]
- National Institute of General Medicine Sciences of the National Institutes of Health [U54GM104940]
- Stand-Up-to-Cancer Colorectal Dream Team Grant
- Guo Shu Shi Fund
- Karen Guo Colon Cancer Research Fund
- Stone Research Fund
- Douglas Gray Woodruff Chair Fund
- Eli Lily Company
- Genentech
- Pfizer
- Sanofi
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In patients with metastatic colorectal cancer, high levels of plasma IGFBP-3 and low levels of IGFBP-7 were associated with longer overall survival and progression-free survival. Extreme levels of adiponectin were linked to shorter progression-free survival, suggesting potential implications for prognostic and therapeutic innovation.
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; P-nonlinearity < .001) and for PFS of 0.61 (95% CI = 0.45 to 0.82; P-trend = .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; P-trend < .001) and for PFS of 1.38 (95% CI = 1.13 to 1.69; P-trend < .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 (P-nonlinearity = .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.
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