Lipidemic Profile of Patients with Non-Small Cell Lung Cancer and Its Association with Driver Mutations: A Tertiary Center Retrospective Study

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Background: Altered lipid metabolism has been reported in several malignancies, but its clinical relevance in non-small cell lung cancer (NSCLC) remains uncertain. This study aimed to compare serum lipid parameters between NSCLC patients and healthy controls and to explore their association with histological subtype and selected driver mutations. Methods: We retrospectively analyzed serum total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides (TG) in patients diagnosed with adenocarcinoma or squamous cell carcinoma from 2021 to 2024, alongside a control group of 100 healthy individuals. Statistical comparisons were performed using appropriate parametric or nonparametric tests after normality assessment (Shapiro–Wilk), and p-values were adjusted using the Benjamini–Hochberg false discovery rate (FDR). Results: A total of 160 NSCLC patients were included. Most were male (75.5%) and current or former smokers (96.1%), with a mean age of 70.4 ± 10.3 years. Squamous cell carcinoma was the predominant subtype (64.4%). Hypocholesterolemia was observed in 59.9% of patients, while hypercholesterolemia was less frequent (40.1%). Compared with controls, patients had significantly lower HDL levels (p = 0.007, FDR-adjusted p = 0.024), while other lipid markers showed no statistically significant differences after correction for multiple testing. Differences between adenocarcinoma and squamous cell carcinoma were not statistically significant. Squamous cell carcinoma patients had higher TG but lower TC, LDL, and HDL levels compared with adenocarcinoma. A negative correlation between TG and ROS1 expression remained significant (r = −0.223, FDR-adjusted p = 0.004). Conclusions: In this retrospective, real-world cohort, only HDL levels demonstrated a robust difference between NSCLC patients and controls. Observed associations should be interpreted cautiously due to potential confounding factors and incomplete clinical data inherent to retrospective analyses. Prospective studies are needed to clarify whether lipid alterations play a biological or prognostic role in NSCLC.

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