Molecular Diagnostics

Biomarker measurement in non-invasively sampled colorectal mucus as a novel approach to colorectal cancer detection: screening and triage implications

Abstract

Background

Faecal tests are widely applied for colorectal cancer (CRC) screening and considered for triaging symptomatic patients with suspected CRC. However, faecal tests can be inconvenient, complex and expensive. Colorectal mucus (CM) sampled using our new patient-friendly non-invasive technique is rich in CRC biomarkers. This study aimed to evaluate diagnostic accuracy of CRC detection by measuring protein biomarkers in CM.

Methods

Colorectal mucus samples were provided by 35 healthy controls, 62 CRC-free symptomatic patients and 40 CRC patients. Biomarkers were quantified by ELISA. Diagnostic performances of haemoglobin, C-reactive protein, tissue inhibitor of metalloproteinases-1, M2-pyruvate kinase, matrix metalloproteinase-9, peptidyl arginine deiminase-4, epidermal growth factor receptor, calprotectin and eosinophil-derived neurotoxin were assessed using receiver operating characteristic (ROC) curve analysis.

Results

Colorectal mucus haemoglobin was superior compared to other biomarkers. For haemoglobin, the areas under the curve for discriminating between CRC and healthy groups (‘screening’) and between CRC and symptomatic patients (‘triage’) were 0.921 and 0.854 respectively. The sensitivity of 80.0% and specificities of 94.3% and 85.5% for the two settings respectively were obtained.

Conclusions

Haemoglobin quantification in CM reliably detects CRC. This patient-friendly approach presents an attractive alternative to faecal immunochemical test; however, the two methods need to be directly compared in larger studies.

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Fig. 1
Fig. 2: The presence of malignant cells in CM samples collected from CRC patients (haematoxylin & eosin stain).
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Fig. 4

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Acknowledgements

The authors would like to thank all patients and healthy volunteers for their participation in the study. We are also grateful to Linda Howard, Lucy Pippard, Lesley Nichols and Juliah Jonasi for their excellent assistance in recruiting study participants.

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Authors

Contributions

A.L.: study concept & design, project coordination, laboratory supervision, sample analysis, statistical analysis of the results, manuscript preparation; A.S., J.A., J.M.: patient recruitment, collection and preparation of clinical data; T.B.: sample analysis, cytology reporting; N.F., J.S., A.P.: clinical supervision, patient recruitment, collection and preparation of clinical data. All authors critically reviewed the manuscript and approved its final version for publication.

Corresponding author

Correspondence to Alexandre Loktionov.

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Ethics approval and consent to participate

The protocol of the study was approved by London-South East Research Ethics Committee (16/LO/2273) in accordance with the Declaration of Helsinki. All recruited patients and healthy volunteers provided written informed consent.

Data availability

All data generated by the study are included in the article.

Competing interests

A.L. and T.B. are founders and directors of DiagNodus Ltd. For the remaining authors, there are no conflicts of interest.

Funding information

This study was supported by a grant (ref. 132672) from Innovate UK (UK Technology Strategy Board) to DiagNodus Ltd. Apart from grant provision the funding source was not involved in any aspect of the study.

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Loktionov, A., Soubieres, A., Bandaletova, T. et al. Biomarker measurement in non-invasively sampled colorectal mucus as a novel approach to colorectal cancer detection: screening and triage implications. Br J Cancer 123, 252–260 (2020). https://doi.org/10.1038/s41416-020-0893-8

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