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Systemic inflammation plays a pivotal role in colorectal cancer (CRC) development. Two hallmarks reflect the severity of inflammation—circulating cytokines and nutrition-inflammation biomarkers (NIBs); however, their interplay has not been fully investigated. In total, 128 CRC patients were included. Ten circulating cytokines (TNF-α, TGF-β, IFN-γ, IL-1β, IL-4, IL-6, IL-10, IL-12, IL-13, and IL-23) and NIBs were analyzed. The relationship between cytokines, NIBs, clinicopathological variables, and overall survival (OS) was assessed using univariate and multivariate analyses. Three NIBs (CRP-to-albumin ratio [CAR]), neutrophil-to-lymphocyte ratio [NLR]), and prognostic nutritional index [PNI]) were associated with OS in univariate analysis; however, CAR was better for OS prediction in multivariate analysis (P = 0.015). None of the serum cytokines analyzed showed a significant association with OS. High CAR (≥0.25) and high IL-10 (≥76.6 pg/mL), high NLR (≥8.2) and high IL-23 (≥51.2 pg/mL), and high PNI (≥42.4) and high IL-1β (≥14.3 pg/mL) values were correlated. CAR, NLR, and PNI were not correlated with each other, whereas circulating cytokines were closely interrelated. High CAR was an independent predictor of poor OS in patients with CRC. Different NIBs have unique cytokine profiles, but show no correlation with each other. There is a close association among the circulating cytokines. [ABSTRACT FROM AUTHOR]

The correlations of pretreatment serum concentrations of proinflammatory cytokines such as interleukin (IL)-1 β, IL-6, and tumor necrosis factor- α (TNF α) with the clinicopathologic features and progression of colorectal cancer (CRC) were investigated. The pretreatment serum levels of IL-1 β, IL-6, and TNF α were measured in 164 CRC patients before treatment. The relationships between changes in proinflammatory cytokine and C-reactive protein (CRP) levels and both clinicopathologic variables and disease progression were examined by univariate and multivariate analysis. Advanced tumor stage was associated with a poorer histologic differentiation, higher CRP level, lower albumin level, and inferior progression-free survival rate (PFSR). Furthermore, high levels of CRP (>5 mg/L) were associated with proinflammatory cytokine intensity, defined according to the number of proinflammatory cytokines with levels above the median level (IL-1 β ≥10 pg/mL; IL-6 ≥ 10 pg/mL; and TNF α ≥55 pg/mL). Under different inflammation states, proinflammatory cytokine intensity, in addition to tumor stage, independently predicted PFSR in patients with CRP <5 mg/L, whereas tumor stage was the only independent predictor of PFSR in patients with CRP ≥5 mg/L. Proinflammatory cytokine intensity and the CRP level are clinically relevant for CRC progression. Measurement of IL-1 β, IL-6, and TNF α serum levels may help identify early cancer progression among patients with CRP <5 mg/L in routine practice. [ABSTRACT FROM AUTHOR]