Correction to "Non-invasive Exhaled Breath and Skin Analysis to Diagnose Lung Cancer: Study of Age Effect on Diagnostic Accuracy".

[This corrects the article DOI: 10.1021/acsomega.2c06132.].

Selectivity of Exhaled Breath Biomarkers of Lung Cancer in Relation to Cancer of Other Localizations.

Lung cancer is a leading cause of death worldwide, mostly due to diagnostics in the advanced stage. Therefore, the development of a quick, simple, and non-invasive diagnostic tool to identify cancer is essential. However, the creation of a reliable diagnostic tool is possible only in case of selectivity to other diseases, particularly, cancer of other localizations. This paper is devoted to the study of the variability of exhaled breath samples among patients with lung cancer and cancer of other localizations, such as esophageal, breast, colorectal, kidney, stomach, prostate, cervix, and skin. For this, gas chromatography-mass spectrometry (GC-MS) was used. Two classification models were built. The first model separated patients with lung cancer and cancer of other localizations. The second model classified patients with lung, esophageal, breast, colorectal, and kidney cancer. Mann-Whitney U tests and Kruskal-Wallis H tests were applied to identify differences in investigated groups. Discriminant analysis (DA), gradient-boosted decision trees (GBDT), and artificial neural networks (ANN) were applied to create the models. In the case of classifying lung cancer and cancer of other localizations, average sensitivity and specificity were 68% and 69%, respectively. However, the accuracy of classifying groups of patients with lung, esophageal, breast, colorectal, and kidney cancer was poor.

Non-Invasive Lung Cancer Diagnostics through Metabolites in Exhaled Breath: Influence of the Disease Variability and Comorbidities.

Non-invasive, simple, and fast tests for lung cancer diagnostics are one of the urgent needs for clinical practice. The work describes the results of exhaled breath analysis of 112 lung cancer patients and 120 healthy individuals using gas chromatography-mass spectrometry (GC-MS). Volatile organic compound (VOC) peak areas and their ratios were considered for data analysis. VOC profiles of patients with various histological types, tumor localization, TNM stage, and treatment status were considered. The effect of non-pulmonary comorbidities (chronic heart failure, hypertension, anemia, acute cerebrovascular accident, obesity, diabetes) on exhaled breath composition of lung cancer patients was studied for the first time. Significant correlations between some VOC peak areas and their ratios and these factors were found. Diagnostic models were created using gradient boosted decision trees (GBDT) and artificial neural network (ANN). The performance of developed models was compared. ANN model was the most accurate: 82-88% sensitivity and 80-86% specificity on the test data.

Non-invasive Exhaled Breath and Skin Analysis to Diagnose Lung Cancer: Study of Age Effect on Diagnostic Accuracy.

Development of simple, fast, and non-invasive tests for lung cancer diagnostics is essential for clinical practice. In this paper, exhaled breath and skin were studied as potential objects to diagnose lung cancer. The influence of age on the performance of diagnostic models was studied. Gas chromatography in combination with mass spectrometry (MS) was used to analyze the exhaled breath of 110 lung cancer patients and 212 healthy individuals of various ages. Peak area ratios of volatile organic compounds (VOCs) were used for data analysis instead of VOC peak areas. Various machine learning algorithms were applied to create diagnostic models, and their performance was compared. The best results on the test data set were achieved using artificial neural networks (ANNs): classification of patients with lung cancer and young healthy volunteers: 88 ± 4% sensitivity and 83 ± 3% specificity; classification of patients with lung cancer and old healthy individuals: 81 ± 3% sensitivity and 85 ± 1% specificity. The difference between performance of models based on young and old healthy groups was minor. The results obtained have shown that metabolic dysregulation driven by the disease biology is too high, which significantly overlaps the age effect. The influence of tumor localization and histological type on exhaled breath samples of lung cancer patients was studied. Statistically significant differences between some parameters in these samples were observed. A possibility of assessing the disease status by skin analysis in the Zakharyin-Ged zones using an electronic nose based on the quartz crystal microbalance sensor system was evaluated. Diagnostic models created using ANNs allow us to classify the skin composition of patients with lung cancer and healthy subjects of different ages with a sensitivity of 69 ± 2% and a specificity of 68 ± 8% for the young healthy group and a sensitivity of 74 ± 7% and a specificity of 66 ± 6% for the old healthy group. Primary results of skin analysis in the Zakharyin-Ged zones for the lung cancer diagnosis have shown its utility, but further investigation is required to confirm the results obtained.

Exhaled breath analysis using GC-MS and an electronic nose for lung cancer diagnostics.

Exhaled breath analysis is an interesting and promising approach for the diagnostics of various diseases. Being non-invasive, convenient and simple, this approach has tremendous potential utility for further translation into clinical practice. In this study, gas chromatography-mass spectrometry (GC-MS) and quartz microbalance sensor-based "electronic nose" were applied for analysis of the exhaled breath of 40 lung cancer patients and 40 healthy individuals. It was found that the electronic nose was unable to distinguish the samples of different groups. However, the application of GC-MS allowed identifying statistically significant differences in compound peak areas and their ratios for investigated groups. Diagnostic models were created using random forest classifier based on peak areas and their ratios with the sensitivity and specificity of peak areas (ratios) of 85.7-96.5% (75.0-93.1%) and 73.3-85.1% (90.0-92.5%) on training data and 63.6-75.0% (72.7-100.0%) and 50.0-69.2% (76.9-84.6%) on test data, respectively. The exhaled breath samples of lung cancer patients and healthy volunteers could be distinguished by GC-MS with the use of individual compounds, but application of their ratios could help to determine specific differences between investigated groups and the level the influence of individual metabolism features alternating from one person to another as well as daily instrument reproducibility deviations. The electronic nose has to be significantly improved to apply it to lung cancer diagnostics of exhaled breath analysis and the influence of water vapour has to be lowered to increase the sensitivity of the sensors to detect lung cancer biomarkers.

Study of confounding factors influence on lung cancer diagnostics effectiveness using gas chromatography-mass spectrometry analysis of exhaled breath.

Aim: The purpose of this study was to estimate volatile organic compounds (VOCs) ability to distinguish exhaled breath samples of lung cancer patients and healthy volunteers and to assess the effect of smoking status and gender on parameters. Patients & methods: Exhaled breath samples of 40 lung cancer patients and 40 healthy individuals were analyzed using gas chromatography-mass spectrometry. Influence of other factors on the exhaled breath VOCs profile was investigated. Results: Some parameters correlating with the disease status were affected by other factors. Excluding these parameters allows creating a logistic regression diagnostic model with 83% sensitivity and 81% specificity. Conclusion: Influence of other factors on the exhaled breath VOCs profile has to be taken into account to avoid misleading results.

Investigation of different approaches for exhaled breath and tumor tissue analyses to identify lung cancer biomarkers.

Development of early noninvasive methods for lung cancer diagnosis is among the most promising technologies, especially using exhaled breath as an object of analysis. Simple sample collection combined with easy and quick sample preparation, as well as the long-term stability of the samples, make it an ideal choice for routine analysis. The conditions of exhaled breath analysis by preconcentrating volatile organic compounds (VOCs) in sorbent tubes, two-stage thermal desorption and gas-chromatographic determination with flame-ionization detection have been optimized. These conditions were applied to estimate differences in exhaled breath VOC profiles of lung cancer patients and healthy volunteers. The combination of statistical methods was used to evaluate the ability of VOCs and their ratios to classify lung cancer patients and healthy volunteers. The performance of diagnostic models on the test data set was greater than 90 % for both VOC peak areas and their ratios. Some of the exhaled breath samples were analyzed using gas chromatography coupled with mass spectrometry (GC-MS) to identify VOCs present in exhaled breath at lower concentration levels. To confirm the endogenous origin of VOCs found in exhaled breath, GC-MS analysis of tumor tissues was conducted. Some of the VOCs identified in exhaled breath were found in tumor tissues, but their frequency of occurrence was significantly lower than in the case of exhaled breath.