In Cancer discovery ; h5-index 105.0
Liver cancer is a major cause of cancer mortality worldwide. Screening individuals at high-risk, including those with cirrhosis and viral hepatitis, provides an avenue for improved survival, but current screening methods are inadequate. In this study, we used whole-genome cell-free DNA fragmentome analyses to evaluate 724 individuals from the US, EU, or Hong Kong with hepatocellular carcinoma (HCC) or who were at average or high-risk for HCC. Using a machine learning model that incorporated multi-feature fragmentome data, the sensitivity for detecting cancer was 88% in an average risk population at 98% specificity, and 85% among high-risk individuals at 80% specificity. We validated these results in an independent population. cfDNA fragmentation changes reflected genomic and chromatin changes in liver cancer, including from transcription factor binding sites. These findings provide a biological basis for changes in cfDNA fragmentation in patients with liver cancer and provide an accessible approach for non-invasive cancer detection.
Foda Zachariah H, Annapragada Akshaya V, Boyapati Kavya, Bruhm Daniel C, Vulpescu Nicholas A, Medina Jamie E, Mathios Dimitrios, Cristiano Stephen, Niknafs Noushin, Luu Harry T, Goggins Michael G, Anders Robert A, Sun Jing, Mehta Shruti H, Thomas David L, Kirk Gregory D, Adleff Vilmos, Phallen Jillian, Scharpf Robert B, Kim Amy K, Velculescu Victor E
2022-Nov-18
