Pancreatic ductal adenocarcinoma can be detected by analysis of volatile organic compounds (VOCs) in alveolar air

Abstract

Background: In the last decade many studies showed that the exhaled breath of subjects suffering from several pathological conditions has a peculiar volatile organic compound (VOC) profile. The objective of the present work was to analyse the VOCs in alveolar air to build a diagnostic tool able to identify the presence of pancreatic ductal adenocarcinoma in patients with histologically confirmed disease.

Methods: The concentration of 92 compounds was measured in the end-tidal breath of 65 cases and 102 controls. VOCs were measured with an ion-molecule reaction mass spectrometry. To distinguish between subjects with pancreatic adenocarcinomas and controls, an iterated Least Absolute Shrinkage and Selection Operator multivariate Logistic Regression model was elaborated.

Results: The final predictive model, based on 10 VOCs, significantly and independently associated with the outcome had a sensitivity and specificity of 100 and 84% respectively, and an area under the ROC curve of 0.99. For further validation, the model was run on 50 other subjects: 24 cases and 26 controls; 23 patients with histological diagnosis of pancreatic adenocarcinomas and 25 controls were correctly identified by the model.

Conclusions: Pancreatic cancer is able to alter the concentration of some molecules in the blood and hence of VOCs in the alveolar air in equilibrium. The detection and statistical rendering of alveolar VOC composition can be useful for the clinical diagnostic approach of pancreatic neoplasms with excellent sensitivity and specificity.

Keywords: Alveolar air; IMR-MS; LASSO logistic regression; Pancreatic adenocarcinoma; Volatile organic compounds.

Fig. 1

Alveolar (unbroken line) and environmental (dotted line) concentrations used for the statistics (70 groups of molecules): molecules which were significantly more present in the environmental air than in the alveolar air have been excluded (data are reported in ppb). The 22 molecules excluded were the following: M19, M26, M27, M28, M31, M32, M45, M48, M49, M73, M92, M97, M98, M102, M103, M104, M105, M116, M117, M18, M120 and M121

Fig. 2

Sensitivity and specificity curves for the Ductal Adenocarcinoma Model and Receiver Operating Characteristic curve (area under ROC = 0.9879)