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. 2022 Nov;18(35):3895-3912.
doi: 10.2217/fon-2022-1041. Epub 2022 Dec 16.

Multimodal analysis of ctDNA methylation and fragmentomic profiles enhances detection of nonmetastatic colorectal cancer

Huu Thinh Nguyen  1 , Le Anh Khoa Huynh  2   3 , Trieu Vu Nguyen  4 , Duc Huy Tran  1 , Thuy Thi Thu Tran  2   5 , Nguyen Duy Khang Le  2   5 , Ngoc-An Trinh Le  1 , Truong-Vinh Ngoc Pham  1 , Minh-Triet Le  1 , Thi Mong Quynh Pham  2   5 , Trong Hieu Nguyen  2   5 , Thien Chi Van Nguyen  2   5 , Thanh Dat Nguyen  2   5 , Bui Que Tran Nguyen  2   5 , Minh-Duy Phan  2   5 , Hoa Giang  2   5 , Le Son Tran  2   5
Affiliations

Multimodal analysis of ctDNA methylation and fragmentomic profiles enhances detection of nonmetastatic colorectal cancer

Huu Thinh Nguyen et al. Future Oncol. 2022 Nov.

Abstract

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.

Keywords: H2O deep neural network; bisulfite sequencing; cfDNA; colorectal cancer; ctDNA; early cancer detection; fragment length; next-generation sequencing; targeted methylation; whole-genome methylation.

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.

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