ObjectiveA large portion of non-metastatic colorectal cancers (non-mCRCs) recur after curative surgery. In addition to the traditional tumor-related factors, host-related factors are also required to accurately predict prognosis. A few studies have shown an association between the serum lipid profile and the survival and treatment response of patients with colorectal cancer. MethodsWe retrospectively evaluated the prognostic significance of the preoperative serum lipid profile [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C)] in patients with non-mCRC treated with curative surgery. The Spearman rank correlation test was used to analyze associations between lipid levels and categorical variables. Lipid levels were modeled as four equal-sized quartiles based on the distribution among the whole cohort. Kaplan-Meier curves were used to estimate survival probabilities, and the log-rank test was used to detect differences between them. Multivariate fractional polynomial (MFP) analysis was used to model any non-linear effects and avoid categorization. To evaluate the added prognostic value of lipids, the predictive power of two models (with and without lipids as covariates) was compared by using Harrell's C-statistic and the Akaike information criterion (AIC). ResultsA total of 266 patients with non-mCRC were enrolled in the present study. Spearman rank correlation test showed that TG levels inversely correlated with N stage (r = −0.20, P = 0.00) and Tumor-Node-Metastasis (TNM) stage (r = −0.19, P = 0.00). HDL-C levels positively correlated with perineural invasion (PNI) (r = 0.15, P = 0.02), and LDL-C levels inversely correlated with lymphovascular invasion (LVI) (r = −0.12, P = 0.04). None of the four lipids predicted overall survival (OS) in univariate or multivariate analyses adjusted for age, gender, T stage, N stage, TNM stage, histological grade, tumor deposits, LVI, PNI, and adjuvant treatment (all P > 0.05). In agreement, the Kaplan-Meier curves for OS according to the lipid quartiles were not significantly different, as confirmed by the log-rank test (all P > 0.05). MFP analysis also found no significant associations between lipid levels and OS (all P > 0.05). A prognostic model that included lipids had a higher Harrell's C-statistic and a lower AIC value than did a model that did not include lipids (for Harrell's C-statistic: 0.82 vs. 0.77; for AIC: 398 vs. 432). ConclusionMeasuring preoperative serum lipid levels may be a simple and cost-effective way of increasing prognostic accuracy in patients with non-mCRC treated with curative surgery.