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ScanTecc classifies primary cancers via cell-free extrachromosomal circular DNA in peripheral blood

By Jingwen Fang, Yehong Xu, Jing Wang, Benjie Shan, Kaiyang Ding, Shouzhen Li, Qiaoni Yu, Wen Zhang, Yunying shao, Jiaxuan Yang, Ke Liu, Guangtao Xu, Xinfeng Yao, Ruoming Sun, Mengyuan Zhang, Zhihong Zhang, Yueyin Pan, Chuang Guo, Kun Qu

Posted 27 Jun 2022
medRxiv DOI: 10.1101/2022.06.24.22276859

Extrachromosomal circular DNA (eccDNA) is gaining substantial attention in basic and clinical research for its contribution to tumor heterogeneity, biogenesis, and evolution. However, its presence and molecular features in peripheral blood from cancer patients are poorly understood. Here, we demonstrated the existence of eccDNA molecules in cancer patients' plasma using atomic-force microscopy and high throughput sequencing technology. We then developed a method named ScanTecc (Screening cancer Types with cell-free eccDNA) that integrates cell-free circular DNA sequencing and machine learning approaches for cancer patient screening and classification. We applied ScanTecc on a total of 413 patients with multiple types of human primary cancers and 52 healthy individuals and found a significantly greater number and more extended size of eccDNAs in patients' peripheral blood. ScanTecc accurately distinguished cancer patients (including early stages I and II) from healthy individuals with an overall prediction rate of 0.85 and identified distinct cancer types with an overall prediction rate of 0.84. Our study provides evidence for a non-invasive approach potentially applicable for early detection of cancer patients in clinics.

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