Confounding effect of benign pulmonary diseases in selecting volatile organic compounds as markers of lung cancer

Abstract

Lung cancer (LC) is a leading cause of cancer-related morbidity and mortality globally, and exhaled breath testing has been considered as a fast, convenient and non-invasive way to diagnose LC in its early stages. Volatile organic compounds (VOCs), as markers of LC in exhaled breath, have been widely investigated for cancer diagnosis. However, few studies have reported on the interference of benign pulmonary diseases (BPD) in the selection of VOC markers for LC. During this study, 207 samples were analyzed using thermal desorption instrumentation/gas chromatography/mass spectrometry (TD-GCMS) to detect C₆-C₃₀ VOCs, and all samples were divided into four groups: LC group, BPD group, lung disease (LD) group (including LC group and BPD group) and healthy group. To make up for the deficiency of detecting low carbon hydrocarbons (<C₆), 277 samples were analyzed using solid-phase micro-extraction/gas chromatography/mass spectrometry (SPME-GCMS), divided among the four groups. VOC markers were selected by reference to the receiver operating characteristics curve. With the comparisons among the LC group, BPD group and healthy group from TD-GCMS and SPME-GCMS results, we found that exhaled VOCs are capable of discriminating LC group versus healthy group and BPD group versus healthy group with a consistency of 70%-80%. However, no VOCs can be selected with good discrimination capability between the LC group and BPD group, indicating that BPD interferes significantly in VOC marker selection for LC. To discriminate breath samples from the LD group and healthy group, 11 VOCs, including ten selected from TD-GCMS and one from SPME-GCMS, were chosen as markers for LD diagnosis. The sensitivity, specificity and overall accuracy of the diagnostic model established using ten VOCs were 80.8%, 84% and 82.7%, and those of the model established by using one VOC were 75.6%, 78.9% and 76.7%. These results validate that LD patients can be effectively discriminated and diagnosed using exhaled VOC analysis. (Clinical trial registration number: ChiCTR-DCD-15007106.).