Original article

Significant differences in volatile organic compounds and interleukin-12 (IL-12) serum levels between lung cancer patients and healthy controls: a cross-sectional study

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Abstract

Aim: To explore differences in exhaled volatile organic compounds (VOCs) and serum interleukin-12 (IL-12) levels between lung cancer patients and healthy controls, and their potential relationship with tumour-related metabolic and systemic immune alterations.

Methods: A cross-sectional study was conducted involving lung cancer patients and healthy controls. Exhaled breath samples were analysed using the µβreath sensor to quantify VOCs, including total volatile organic compounds (TVOC)(1), TVOC(2), acetone, formaldehyde, toluene, hexane, and methane. Serum IL‑12 levels were measured via ELISA. Significant limitations such as age mismatch, unvalidated sensor data, and potential confounders (smoking, chemotherapy, diet, environmental VOCs) were acknowledged.

Results: Lung cancer patients exhibited significantly higher TVOC(1) and TVOC(2) levels, and higher acetone levels, while formaldehyde, toluene, hexane, and methane levels were lower than in controls. Serum IL‑12 levels were markedly lower in patients, reflecting systemic immune modulation rather than direct diagnostic specificity. ROC analysis indicated high sensitivity for certain VOCs, but specificity remained limited, suggesting that these markers were exploratory rather than definitive diagnostic tools. No significant correlation was observed between VOCs and IL‑12 levels.

Conclusion: Differences in exhaled VOC profiles and serum IL-12 levels provide preliminary insight into tumour-related metabolic and immune alterations in lung cancer. However, due to major methodological limitations, particularly age mismatch and incomplete sensor validation, these findings should be interpreted with caution. Exhaled VOCs and IL-12 should be considered hypothesis-generating exploratory biomarkers that require validation in larger, age-matched cohorts using gold-standard analytical techniques and multivariate modelling.

Keywords: biomarkers, breathe tests, interleukin-12, lung neoplasms, volatile organic compounds