Aims: Early detection of colorectal cancer (CRC) provides substantially better survival rates. This study aimed to develop a blood-based screening assay named SPOT-MAS (‘screen for the presence of tumor by DNA methylation and size’) for early CRC detection with high accuracy. Methods: Plasma cell-free DNA samples from 159 patients with nonmetastatic CRC and 158 healthy controls were simultaneously analyzed for fragment length and methylation profiles. We then employed a deep neural network with fragment length and methylation signatures to build a classification model. Results: The model achieved an area under the curve of 0.989 and a sensitivity of 96.8% at 97% specificity in detecting CRC. External validation of our model showed comparable performance, with an area under the curve of 0.96. Conclusion: SPOT-MAS based on integration of cancer-specific methylation and fragmentomic signatures could provide high accuracy for early-stage CRC detection.

Plain language summary

A novel blood test for early detection of colorectal cancer. Colorectal cancer is a cancer of the colon or rectum, located at the lower end of the digestive tract. The early detection of colorectal cancer can help people with the disease have a higher chance of survival and a better quality of life. Current screening methods can be invasive, cause discomfort or have low accuracy; therefore newer screening methods are needed. In this study we developed a new screening method, called SPOT-MAS, which works by measuring the signals of cancer DNA in the blood. By combining different characteristics of cancer DNA, SPOT-MAS could distinguish blood samples of people with colorectal cancer from those of healthy individuals with high accuracy.

Tweetable abstract

SPOT-MAS technology combines methylation and fragmentomic signatures of blood-based circulating tumor DNA in a multimodal deep-learning analysis to enable early detection of colorectal cancer with high accuracy.

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Vol. 18, No. 35

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History

Received 20 October 2022

Accepted 25 November 2022

Published online 16 December 2022

Published in print November 2022

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Supplementary data

To view the supplementary data that accompany this paper please visit the journal website at: www.futuremedicine.com/doi/suppl/10.2217/fon-2022-1041

Author contributions

Trieu Vu Nguyen and Bui Que Tran Nguyen did the formal analysis. Huu Thinh Nguyen, Duc Huy Tran, Ngoc-An Trinh Le, Truong-Vinh Ngoc Pham, Minh-Triet Le and Trong Hieu Nguyen performed formal analysis and data curation. Nguyen Duy Khang Le, Thi Mong Quynh Pham and Thien Chi Van Nguyen were responsible for formal analysis, data curation and methodology. Thanh Dat Nguyen ran software and did data curation. Le Anh Khoa Huynh ran software and performed formal analysis and data curation. Thuy Thi Thu Tran wrote and edited the original draft and prepared the final manuscript formatting. Minh-Duy Phan and Hoa Giang carried out data curation and supervision. Le Son Tran was responsible for methodology, reviewed and edited the manuscript, and was responsible for supervision.

Acknowledgments

The authors thank all participants who agreed to take part in this study, as well as all the clinics and hospitals who assisted in patient consultation and sample collection.

Financial & competing interests disclosure

This study was funded by Gene Solutions. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The study was undertaken with the understanding and written consent of each subject. This study methodologies conformed to the standards set by the Declaration of Helsinki. This study was approved by the Ethics Committee of the University of Medical and Pharmacy and Thu Duc Hospital at Ho Chi Minh City, Vietnam.

Data sharing statement

The data presented in this study are available on request from the corresponding author. The data are not publicly available due to ethical regulation.

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