Exhaled metabolic markers and relevant dysregulated pathways of lung cancer: a pilot study

Abstract

Introduction The clinical application of lung cancer detection based on breath test is still challenging due to lack of predictive molecular markers in exhaled breath. This study explored potential lung cancer biomarkers and their related pathways using a typical process for metabolomics investigation. Material and methods Breath samples from 60 lung cancer patients and 176 healthy people were analyzed by GC-MS. The original data were GC-MS peak intensity removing background signal. Differential metabolites were selected after univariate statistical analysis and multivariate statistical analysis based on OPLS-DA and Spearman rank correlation analysis. A multivariate PLS-DA model was established based on differential metabolites for pattern recognition. Subsequently, pathway enrichment analysis was performed on differential metabolites. Results The discriminant capability was assessed by ROC curve of whom the average AUC and average accuracy in 100-fold cross validations were 0.871 and 0.787, respectively. Eight potential biomarkers were involved in a total of 18 metabolic pathways. Among them, 11 metabolic pathways have p -value smaller than .1. Discussion Some pathways among them are related to risk factors or therapies of lung cancer. However, more of them are dysregulated pathways of lung cancer reported in studies based on genome or transcriptome data. Conclusion We believe that it opens the possibility of using metabolomics methods to analyze data of exhaled breath and promotes involvement of knowledge dataset to cover more volatile metabolites. Clinical significance Although a series of related research reported diagnostic models with highly sensitive and specific prediction, the clinical application of lung cancer detection based on breath test is still challenging due to disease heterogeneity and lack of predictive molecular markers in exhaled breath. This study may promote the clinical application of this technique which is suitable for large-scale screening thanks to its low-cost and non-invasiveness. As a result, the mortality of lung cancer may be decreased in future. Key messages In the present study, 11 pathways involving 8 potential biomarkers were discovered to be dysregulated pathways of lung cancer. We found that it is possible to apply metabolomics methods in analysis of data from breath test, which is meaningful to discover convinced volatile markers with definite pathological and histological significance.

Lipid Peroxidation Produces a Diverse Mixture of Saturated and Unsaturated Aldehydes in Exhaled Breath That Can Serve as Biomarkers of Lung Cancer—A Review

“…In 2007, Chen et al highlighted the VOCs present in the headspace, and in another, much larger, study with 160 LC patients in 2021, found hexanal to once again rise to the level of a biomarker of LC [93]. Rudnicka et al [77], Gashimova et al [94], and Zou et al [100] also reported hexanal to be an EB biomarker of LC. Whereas Kischkel et al measured hexanal to have a greater median concentration in the EB of LC patients (0.59 nmol/L) than that of healthy smokers (0.31 nmol/L), the concentration in LC patients was less than the median concentration they measured in HCs (0.63 nmol/L) [68].…”

GC-MS-based metabolomics of volatile organic compounds in exhaled breath: applications in health and disease. A review

“…Twenty-two discriminative VOCs were annotated, styrene being also found downregulated in LC patients who responded partially to treatment or remained stable ( Supplementary Table S3 ), along with two other VOCs (dodecane, 4-methyl and α-phellandrene) ( Nardi-Agmon et al, 2016 ). The second study ( Zou et al, 2022 ) selected 31 VOCs as biomarkers in the univariate analysis (UVA), which showed 0.787 AUC in the multivariate analysis (MVA) after cross-validation. Additionally, eight VOCs were found to be involved in a total of 18 metabolic pathways, of which 11 were significantly altered.…”

“…Although many studies propose potential biomarkers for various pathologies, the expected clinical application of breath tests has not progressed as expected ( Buszewski et al, 2007 ; Sharma et al, 2023 ). Additionally, the link between potential biomarkers and specific pathologies is not clear ( Haick et al, 2014 ; Zou et al, 2022 ).…”

Exploring the Utility of Expanded Clinical Exome Sequencing in Cancer Patients with Pesticide Exposure: Insights from Blood Samples

“…These disruptions can signi cantly contribute to the development and progression of various diseases, including cancer [19][20][21][22][23] . Indeed, identifying inherited mutations in cancer-related pathways can provide valuable insights into the mechanisms involved in carcinogenesis, particularly in cases where patients have a comprehensive expositional history 24 . These inherited mutations become particularly relevant when dealing with extensive datasets, such as those generated from genome and exome sequencing 25,26 .…”