Detecting Colorectal Adenomas and Cancer Using Volatile Organic Compounds in Exhaled Breath: A Proof-of-Principle Study to Improve Screening

Cheng, Hao; Vorstenbosch, Robert W.R. van; Pachen, D. M. F. A.; Meulen, Lonne W.T.; Straathof, Jan Willem; Dallinga, Jan W.; Jonkers, Daisy; Masclee, Ad; Schooten, Frederik‐Jan van; Mujagic, Zlatan; Smolinska, Agnieszka

doi:10.14309/ctg.0000000000000518

Cited by 11 publications

(10 citation statements)

References 48 publications

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“…The majority (n = 68) analyzed CRC cases compared to controls and eight studies included adenomas [ 33 , 36 , 45 , 68 , 69 , 96 , 97 , 98 ]. VOCs were analyzed in several biological matrices, including feces (n = 11) [ 31 , 33 , 36 , 49 , 52 , 63 , 87 , 89 , 90 , 92 , 98 ], urine (n = 9) [ 34 , 35 , 62 , 65 , 74 , 75 , 78 , 80 , 82 ], breath (n = 10) [ 28 , 29 , 40 , 51 , 60 , 61 , 70 , 72 , 85 , 96 ], blood (n = 21) [ 37 , 38 , 43 , 44 , 45 , 46 , 48 , 53 , 56 , 57 , 66 , 67 ,…”

Section: Resultsmentioning

confidence: 99%

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Systematic Review: Contribution of the Gut Microbiome to the Volatile Metabolic Fingerprint of Colorectal Neoplasia

et al. 2022

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Colorectal cancer (CRC) has been associated with changes in volatile metabolic profiles in several human biological matrices. This enables its non-invasive detection, but the origin of these volatile organic compounds (VOCs) and their relation to the gut microbiome are not yet fully understood. This systematic review provides an overview of the current understanding of this topic. A systematic search using PubMed, Embase, Medline, Cochrane Library, and the Web of Science according to PRISMA guidelines resulted in seventy-one included studies. In addition, a systematic search was conducted that identified five systematic reviews from which CRC-associated gut microbiota data were extracted. The included studies analyzed VOCs in feces, urine, breath, blood, tissue, and saliva. Eight studies performed microbiota analysis in addition to VOC analysis. The most frequently reported dysregulations over all matrices included short-chain fatty acids, amino acids, proteolytic fermentation products, and products related to the tricarboxylic acid cycle and Warburg metabolism. Many of these dysregulations could be related to the shifts in CRC-associated microbiota, and thus the gut microbiota presumably contributes to the metabolic fingerprint of VOC in CRC. Future research involving VOCs analysis should include simultaneous gut microbiota analysis.

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Section: Resultsmentioning

confidence: 99%

“…Observations of SCFAs between studies were inconsistent, but they were repeatedly reported as important VOCs [ 28 , 41 , 72 ]. Similarly, lactic acid was raised in concentration in CRC cases [ 96 ]. No compounds related to the TCA cycle were reported.…”

Section: Resultsmentioning

confidence: 99%

Systematic Review: Contribution of the Gut Microbiome to the Volatile Metabolic Fingerprint of Colorectal Neoplasia

et al. 2022

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“…Among them, 22 studies employed VOC analysis for the diagnosis of colorectal cancer ( 7 , 28 – 46 , 48 , 49 ), 9 studies utilized e-nose technology ( 25 , 26 , 50 – 55 , 58 ), and one study used both VOC analysis and e-nose ( 47 ). In the VOC studies, 10 studies used breath samples ( 7 , 28 – 30 , 38 , 39 , 41 – 43 , 49 ), 6 studies used urine samples ( 32 , 37 , 44 – 46 , 48 ), 5 studies used fecal samples ( 31 , 33 , 35 , 36 , 40 ), and one study used salivary sample ( 34 ). Most studies used MS-based techniques, principally GC-MS (n=7), TD-GC-MS (n=4), FAIM (n=4), and SIFT-MS (n=2).…”

Section: Resultsmentioning

confidence: 99%

“…Due to the lack of standardization in sample collection, handling, and storage, technical barriers exist in measuring and analyzing various VOC characteristics during sampling, whether it involves alveolar air, urine, or feces. In several studies, exhaled breath was collected into a bag and subsequently analyzed ( 28 , 29 , 33 , 38 – 40 , 42 , 50 ). The use of bag collection aligns more closely with real-world medical applications.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic performance of volatile organic compounds analysis and electronic noses for detecting colorectal cancer: a systematic review and meta-analysis

Wang,

Fang,

Tan

et al. 2024

Front. Oncol.

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IntroductionThe detection of Volatile Organic Compounds (VOCs) could provide a potential diagnostic modality for the early detection and surveillance of colorectal cancers. However, the overall diagnostic accuracy of the proposed tests remains uncertain.ObjectiveThis systematic review is to ascertain the diagnostic accuracy of using VOC analysis techniques and electronic noses (e-noses) as noninvasive diagnostic methods for colorectal cancer within the realm of clinical practice.MethodsA systematic search was undertaken on PubMed, EMBASE, Web of Science, and the Cochrane Library to scrutinize pertinent studies published from their inception to September 1, 2023. Only studies conducted on human subjects were included. Meta-analysis was performed using a bivariate model to obtain summary estimates of sensitivity, specificity, and positive and negative likelihood ratios. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was deployed for quality assessment. The protocol for this systematic review was registered in PROSPERO, and PRISMA guidelines were used for the identification, screening, eligibility, and selection process.ResultsThis review encompassed 32 studies, 22 studies for VOC analysis and 9 studies for e-nose, one for both, with a total of 4688 subjects in the analysis. The pooled sensitivity and specificity of VOC analysis for CRC detection were 0.88 (95% CI, 0.83-0.92) and 0.85 (95% CI, 0.78-0.90), respectively. In the case of e-nose, the pooled sensitivity was 0.87 (95% CI, 0.83-0.90), and the pooled specificity was 0.78 (95% CI, 0.62-0.88). The area under the receiver operating characteristic analysis (ROC) curve for VOC analysis and e-noses were 0.93 (95% CI, 0.90-0.95) and 0.90 (95% CI, 0.87-0.92), respectively.ConclusionThe outcomes of this review substantiate the commendable accuracy of VOC analysis and e-nose technology in detecting CRC. VOC analysis has a higher specificity than e-nose for the diagnosis of CRC and a sensitivity comparable to that of e-nose. However, numerous limitations, including a modest sample size, absence of standardized collection methods, lack of external validation, and a notable risk of bias, were identified. Consequently, there exists an imperative need for expansive, multi-center clinical studies to elucidate the applicability and reproducibility of VOC analysis or e-nose in the noninvasive diagnosis of colorectal cancer.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/#recordDetails, identifier CRD42023398465.

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“…In a multicenter prospective study, breath samples from 382 FIT-positive Dutch patients were collected. A biomarker profile was established based on ten discriminatory VOCs and this profile could discriminate CRCs ( N =30) from controls ( N =84) with a sensitivity and specificity of 80 and 70%, respectively 52 . Markar et al .…”

Section: Introductionmentioning

confidence: 99%

Application and development of noninvasive biomarkers for colorectal cancer screening: a systematic review

Song¹,

Wang

et al. 2023

International Journal of Surgery

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Background: Colorectal cancer (CRC) is the second most common cause of cancer-related death (9.4% of the 9.9 million cancer deaths). However, CRC develops slowly, and early detection and intervention can effectively improve the survival rate and quality of life. Although colonoscopy can detect and diagnose CRC, it is unsuitable for CRC screening in average-risk populations. Some commercial kits based on DNA mutation or methylation are approved for screening, but the low sensitivity for advanced adenoma or early-stage CRC would limit the applications. Main results: Recently, researchers have focused on developing noninvasive or minimally invasive, easily accessible biomarkers with higher sensitivity and accuracy for CRC screening. Numerous reports describe advances in biomarkers, including DNA mutations and methylation, mRNA and miRNA, gut microbes, and metabolites, as well as low-throughput multiomics panels. In small cohorts, the specificity and sensitivity improved when fecal immunochemical testing combined with other biomarkers; further verification in large cohorts is expected. In addition, the continuous improvement of laboratory technology has also improved the sensitivity of detection technology, such as PCR, and the application of CRISPR/Cas technology. Besides, artificial intelligence has extensively promoted the mining of biomarkers. Machine learning was performed to construct a diagnosis model for CRC screening based on the cfDNA fragment features from whole-genome sequencing data. In another study, multiomics markers, including cfDNA, epigenetic, and protein signals, were also discovered by machine learning. Finally, advancements in sensor technology promote the applicability of volatile organic compounds in CRC early detection. Conclusion: Here, the authors review advances in early detection and screening of CRC based on different biomarker types. Most studies reported optimistic findings based on preliminary research, and prospective clinical studies are ongoing. These promising biomarkers are expected to more accurately identify early-stage patients with CRC and be applied in the future.

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Detecting Colorectal Adenomas and Cancer Using Volatile Organic Compounds in Exhaled Breath: A Proof-of-Principle Study to Improve Screening

Cited by 11 publications

References 48 publications

Systematic Review: Contribution of the Gut Microbiome to the Volatile Metabolic Fingerprint of Colorectal Neoplasia

Systematic Review: Contribution of the Gut Microbiome to the Volatile Metabolic Fingerprint of Colorectal Neoplasia

Diagnostic performance of volatile organic compounds analysis and electronic noses for detecting colorectal cancer: a systematic review and meta-analysis

Application and development of noninvasive biomarkers for colorectal cancer screening: a systematic review

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