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

TL;DR

This study found that lung cancer patients have lower HDL cholesterol levels compared to healthy people, and these levels may be linked to tumor type and genetic changes.

Contribution

The study identifies HDL cholesterol as a potential marker for non-small cell lung cancer and its subtypes.

Findings

HDL levels were consistently lower in lung cancer patients compared to healthy controls.

Triglyceride levels showed an inverse association with a specific gene alteration (ROS1).

Squamous tumors had lower HDL levels than adenocarcinomas.

Abstract

This study investigates whether routine blood lipid measurements, such as cholesterol and triglycerides, differ in people with non-small cell lung cancer compared with healthy individuals, and whether these measurements relate to tumor type or key genetic changes that guide modern treatments. Because these tests are inexpensive and widely available, identifying consistent patterns could support future research on simple markers that reflect tumor biology. We reviewed medical records from a tertiary hospital and compared blood lipid levels in lung cancer patients with those of matched controls, and we also examined differences between the main lung cancer subtypes and selected tumor gene alterations. We found that high-density lipoprotein was consistently lower in lung cancer patients, was lower in squamous tumors than in adenocarcinomas, and was lower in patients who died during follow-up. Triglyceride levels showed an inverse association with a specific gene alteration. These findings highlight lipid changes as potential research targets and support larger prospective studies.

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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