Volatile Organic Compounds (VOCs) and Interleukin-23 Levels in Lung Cancer: A Future Biomarker
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Introduction: Lung cancer (LC) is the world's second leading cause of death due to malignancy. In Indonesia, LC is one of the top three malignancies. Volatile organic compounds (VOCs) from the respiratory reflect changes in metabolism caused by disease and may be a biomarker of LC. Interleukin-23 (IL-23) has been known as a pro-inflammatory cytokine in the development and progression of cancer. This study aimed to identify levels of IL-23 and VOCs in LC patients.
Methods: This study involved 40 LC patients and 42 controls. VOCs were taken by the subject exhaling their third deep breath into the sample bag, which was immediately analyzed using an E-nose-based device. As for the IL-23, the cytokine was taken from the blood serum and then analyzed using the ELISA method. Kolmogorov-Smirnov and Shapiro-Wilk tests were performed to test data normality. Mann-Whitney and Kruskal Wallis tests were conducted for variables. Spearman correlation and heat map were used to find the correlation between the observed gases and IL-23.
Results: The concentration of ozone (p = 0.000), ethanol (p = 0.000), formaldehyde (p = 0.000), toluene (p = 0.000), acetone (p = 0.000), ammonia (p = 0.000), ammonium (p = 0.001), nitrogen (p = 0.001) and methane (p = 0.000) in LC group differed with controls. The same outcome was also observed in comparing LC patients and control groups of IL-23 (p = 0.000). Spearman correlation analysis revealed a positive correlation between serum IL-23 with formaldehyde (p = 0.029), toluene (p = 0.014), and ammonia (p = 0.028) and a negative correlation with nitrogen (p = 0.011). Compared to the control group, all types of LC were observed to have higher levels of IL-23. A weak positive correlation was found in formaldehyde (Cv = 0.23), toluene (Cv = 0.23), and ammonia (Cv = 0.13). A weak negative correlation was obtained in acetone (Cv = -0.12), ammonium (Cv = -0.11), and nitrogen dioxide (Cv = 0.23).
Conclusion: Weak linear correlations were obtained between the cytokine and formaldehyde, toluene, ammonia, ammonium, and nitrogen dioxide. A higher IL-23 concentration was observed in the LC group than in the control group. The volatile concentration was significantly different between LC and control groups.
(KPKN) KPKN. Pedoman Nasional Pelayanan Kedokteran Kanker Paru. Jakarta, 2016.
Saalberg Y, Wolff M. VOC Breath Biomarkers in Lung Cancer. Clin Chim Acta 2016; 459: 5–9.
Lawal O, Ahmed WM, Nijsen TME, et al. Exhaled Breath Analysis: A Review of ‘Breath-Taking' Methods for Off-Line Analysis. Metabolomics 2017; 13: 110.
Thriumani R, Zakaria A, Hashim YZH-Y, et al. A Study on Volatile Organic Compounds Emitted by In-Vitro Lung Cancer Cultured Cells using Gas Sensor Array and SPME-GCMS. BMC Cancer 2018; 18: 362.
van der Schee M, Pinheiro H, Gaude E. Breat Biopsy for Early Detection and Precision Medicine in Cancer. Ecancermedicalscience 2018; 12: ed84.
Becker R. Non-Invasive Cancer Detection using Volatile Biomarkers: Is Urine Superior to Breath? Med Hypotheses 2020; 143: 110060.
Santonico M, Lucantoni G, Pennazza G, et al. In Situ Detection of Lung Cancer Volatile Fingerprints using Bronchoscopic Air-Sampling. Lung Cancer 2012; 77: 46–50.
Rocco G, Pennazza G, Santonico M, et al. Breathprinting and Early Diagnosis of Lung Cancer. J Thorac Oncol 2018; 13: 883–894.
Rudnicka J, Kowalkowski T, Buszewski B. Searching for Selected VOCs in Human Breath Samples as Potential Markers of Lung Cancer. Lung Cancer 2019; 135: 123–129.
Chen H, Qi X, Ma J, et al. Breath-Borne VOC Biomarkers for COVID-19. medRxiv 2020; 2020.06.21.20136523.
Saalberg Y, Bruhns H, Wolff M. Photoacoustic Spectroscopy for the Determination of Lung Cancer Biomarkers-A Preliminary Investigation. Sensors (Basel); 17. Epub ahead of print January 2017.
Einoch Amor R, Nakhleh MK, Barash O, et al. Breath Analysis of Cancer in the Present and the Future. Eur Respir Rev; 28. Epub ahead of print June 2019.
Fuchs P, Loeseken C, Schubert JK, et al. Breath Gas Aldehydes as Biomarkers of Lung Cancer. Int J Cancer 2010; 126: 2663–2670.
Ratiu I-A, Ligor T, Bocos-Bintintan V, et al. Mass Spectrometric Techniques for the Analysis of Volatile Organic Compounds Emitted from Bacteria. Bioanalysis 2017; 9: 1069–1092.
Scarlata S, Pennazza G, Santonico M, et al. Exhaled Breath Analysis by Electronic Nose in Respiratory Diseases. Expert Rev Mol Diagn 2015; 15: 933–956.
Hidayat SN, Julian T, Dharmawan AB, et al. Hybrid Learning Method based on Feature Clustering and Scoring for Enhanced COVID-19 Breath Analysis by an Electronic Nose. Artif Intell Med 2022; 129: 102323.
Cam C, Karagoz B, Muftuoglu T, et al. The Inflammatory Cytokine Interleukin-23 is Elevated in Lung Cancer, Particularly Small Cell Type. Contemp Oncol (Poznan, Poland) 2016; 20: 215–219.
Dragonieri S, Quaranta VN, Carratu P, et al. Influence of Age and Gender on the Profile of Exhaled Volatile Organic Compounds Analyzed by an Electronic Nose. Jornal Brasileiro de Pneumologia; 42.
Cauli A, Piga M, Floris A, et al. Current Perspective on the Role of the Interleukin-23/Interleukin-17 Axis in Inflammation and Disease (Chronic Arthritis and Psoriasis). ImmunoTargets Ther 2015; 4: 185–190.
Choi SYC, Collins CC, Gout PW, et al. Cancer-Generated Lactic Acid: A Regulatory, Immunosuppressive Metabolite? J Pathol 2013; 230: 350–355.
Janfaza S, Khorsand B, Nikkhah M, et al. Digging Deeper into Volatile Organic Compounds associated with Cancer. Biol Methods Protoc 2019; 4: bpz014.
Welsby I, Goriely S. Regulation of Interleukin-23 Expression in Health and Disease. Adv Exp Med Biol 2016; 941: 167–189.
Jia X, Tang J, Zhang Y. The Precipitation Chemistry and Acidity over China during 2018. E3S Web Conf; 136, https://doi.org/10.1051/e3sconf/201913606020 (2019).
Oguma T, Nagaoka T, Kurahashi M, et al. Clinical Contributions of Exhaled Volatile Organic Compounds in the Diagnosis of Lung Cancer. PLoS One 2017; 12: e0174802.
Burgos-Barragan G, Wit N, Meiser J, et al. Mammals Divert Endogenous Genotoxic Formaldehyde into One-Carbon Metabolism. Nature 2017; 548: 549–554.
Reingruber H, Pontel LB. Formaldehyde Metabolism and Its Impact on Human Health. Curr Opin Toxicol 2018; 9: 28–34.
Hartwig A, Arand M, Epe B, et al. Mode of action-based risk assessment of genotoxic carcinogens. Arch Toxicol 2020; 94: 1787–1877.
Gashimova E, Temerdashev A, Porkhanov V, et al. Investigation of Different Approaches for Exhaled Breath and Tumor Tissue Analyses to Identify Lung Cancer Biomarkers. Heliyon 2020; 6: e04224.
Li X, Zhu H, Sun W, et al. Role of Glutamine and Its Metabolite Ammonia in Crosstalk of Cancer-Associated Fibroblasts and Cancer Cells. Cancer Cell Int 2021; 21: 479.
Spinelli JB, Yoon H, Ringel AE, et al. Metabolic Recycling of Ammonia via Glutamate Dehydrogenase supports Breast Cancer Biomass. Science 2017; 358: 941–946.
Lane AN, Fan TW-M. Regulation of Mammalian Nucleotide Metabolism and Biosynthesis. Nucleic Acids Res 2015; 43: 2466–2485.
Hosios AM, Hecht VC, Danai LV, et al. Amino Acids Rather than Glucose Account for the Majority of Cell Mass in Proliferating Mammalian Cells. Dev Cell 2016; 36: 540–549.
Vettore L, Westbrook RL, Tennant DA. New Aspects of Amino Acid Metabolism in Cancer. Br J Cancer 2020; 122: 150–156.
Wei Z, Liu X, Cheng C, et al. Metabolism of Amino Acids in Cancer. Frontiers in Cell and Developmental Biology; 8, https://www.frontiersin.org/articles/10.3389/fcell.2020.603837 (2021).
Chang J-E, Lee D-S, Ban S-W, et al. Analysis of Volatile Organic Compounds in Exhaled Breath for Lung Cancer Diagnosis using a Sensor System. Sensors Actuators B Chem 2018; 255: 800–807.
Kallianos A, Tsimpoukis S, Zarogoulidis P, et al. Measurement of Exhaled Alveolar Nitrogen Oxide in Patients with Lung Cancer: A Friend from the Past still Precious Today. Onco Targets Ther 2013; 6: 609–613.
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