IGF-binding proteins, adiponectin and survival in metastatic colorectal cancer: results from CALGB (Alliance)/SWOG 80405
Menée à partir d'échantillons plasmatiques prélevés sur 1 086 patients atteints d'un cancer colorectal métastatique (durée médiane de suivi : 6,2 ans), cette étude évalue l'association entre les niveaux de 5 biomarqueurs impliqués dans la régulation du métabolisme (facteur IGF-I, protéines IGFBP-3 et IGFBP-7, peptide c et adinopectine) et la survie des patients
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)-I, 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 (OS) and progression-free survival (PFS). P values are two-sided.
Results : Median follow-up for 1,086 patients was 6.2 years. Compared to 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, Pnon-linearity < .001) and for PFS of 0.61 (95% CI = 0.45 to 0.82, Ptrend = .003). Compared to patients in the lowest IGFBP-7 quintile, patients in the highest IGFBP-7 quintile experienced an adjusted HR 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-I were not associated with patient outcomes. Adiponectin was not associated with OS; there was a non-linear U-shaped association between adiponectin and PFS (Pnon-linearity = .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.
JNCI Cancer Spectrum , article en libre accès, 2019