Association of Lipid and Inflammatory Profiles With Tumor Stage in Hepatocellular Carcinoma

ABSTRACT Background Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Inflammatory responses and lipid metabolism disorders are known to influence cancer development; however, their combined effects on HCC progression remain unclear. This study examined the associations between lipid profiles and inflammatory markers with HCC stage. Methods In this cross‐sectional study, data from 90 patients with HCC and available Barcelona Clinic Liver Cancer stage information were analyzed. Serum lipid profiles and inflammatory markers were measured, and derived indicators—including non–high‐density lipoprotein cholesterol (non–HDL‐C), the low‐density lipoprotein cholesterol (LDL‐C)‐to‐HDL‐C ratio, the total cholesterol (TC)‐to‐HDL‐C ratio, and the neutrophil‐to‐HDL‐C ratio (NHR)—were calculated. Correlation analysis and logistic regression were performed with adjustment for potential confounders. Interaction analysis was conducted to examine relationships among lipid–inflammatory profiles, with findings validated in an independent cohort of 200 patients with HCC. Results HDL‐C levels were significantly lower in patients with non‐advanced stage tumors (0.81 ± 0.27 vs. 1.15 ± 0.28, p < 0.01). HDL‐C showed a positive correlation with tumor stage ( r = 0.544, p < 0.01), whereas non–HDL‐C, LDL‐to‐HDL ratio, TC‐to‐HDL ratio, and NHR demonstrated negative correlations (r = −0.269, −0.568, −0.382, and −0.432, respectively; all p < 0.05). In univariate logistic regression analysis, higher LDL‐to‐HDL ratio (odds ratio OR = 0.193, 95% confidence interval CI: 0.066–0.562) and higher TC‐to‐HDL ratio (OR = 0.378, 95% CI: 0.195–0.730) were significantly associated with non‐advanced stage, and these associations persisted after adjustment for NHR. Conclusions Lipid‐inflammatory profiles were associated with HCC staging in correlation and partially adjusted regression analyses and showed apparent discriminative performance in ROC analysis. However, no independent predictors were identified in the fully adjusted multivariable model. These findings should be considered exploratory and hypothesis‐generating, suggesting that lipid‐inflammatory profiles may reflect staging‐related metabolic and inflammatory alterations rather than serve as independent staging markers. Further validation in large prospective studies is required.