Volatile organic compounds in breath can serve as a non-invasive diagnostic biomarker for the detection of advanced adenomas and colorectal cancer

Abstract

Background: Colorectal cancer (CRC) is the third most common cancer diagnosis in the Western world.

Aim: To evaluate exhaled volatile organic compounds (VOCs) as a non-invasive biomarker for the detection of CRC and precursor lesions using an electronic nose.

Methods: In this multicentre study adult colonoscopy patients, without inflammatory bowel disease or (previous) malignancy, were invited for breath analysis. Two-thirds of the breath tests were randomly assigned to develop training models which were used to predict the diagnosis of the remaining patients (external validation). In the end, all data were used to develop final-disease models to further improve the discriminatory power of the algorithms.

Results: Five hundred and eleven breath samples were collected. Sixty-four patients were excluded due to an inadequate breath test (n = 51), incomplete colonoscopy (n = 8) or colitis (n = 5). Classification was based on the most advanced lesion found; CRC (n = 70), advanced adenomas (AAs) (n = 117), non-advanced adenoma (n = 117), hyperplastic polyp (n = 15), normal colonoscopy (n = 125). Training models for CRC and AAs had an area under the curve (AUC) of 0.76 and 0.71 and blind validation resulted in an AUC of 0.74 and 0.61 respectively. Final models for CRC and AAs yielded an AUC of 0.84 (sensitivity 95% and specificity 64%) and 0.73 (sensitivity and specificity 79% and 59%) respectively.

Conclusions: This study suggests that exhaled VOCs could potentially serve as a non-invasive biomarker for the detection of CRC and AAs. Future studies including more patients could further improve the discriminatory potential of VOC analysis for the detection of (pre-)malignant colorectal lesions. (https://clinicaltrials.gov Identifier NCT03488537).

Figure 1

Electronic nose used in the study; the Aeonose (The eNose Company). Patients inhale through a carbon filter to prevent the entry of nonfiltered environmental air and breathe into the device through a disposable mouthpiece while wearing a nose clip

Figure 2

Flowchart. AA, advanced adenoma; CRC, colorectal cancer; HP, hyperplastic polyp; N, number; NA, non‐advanced adenoma

Figure 3

ROC curve plus scatter plot of the final disease‐specific model for colorectal cancer (CRC). In the scatter plot the individual e‐nose value of each patient and control is plotted. Patients with histopathologically confirmed CRC are represented with a red square and all healthy controls are represented with a green dot. The blue line at −0.03 indicates the cut‐off point used in this study. All patients with a value greater than −0.03 were indicated as positive for CRC by the e‐nose