Development and clinical applications of liquid biopsy assays in cancer screening

Liquid biopsy has become a research focus and a hotspot of product development in cancer screening. With the rapid development of molecular biology technology, many new markers have been identified and developed in cancer screening tests in recent years. This article reviews the development of novel liquid biopsy-based markers in cancer screening, including methylation, hydroxymethylation, mutation, copy number variation, and microRNA (miRNA), with specific focuses on clinical trials and studies from approved cancer screening assays or tests under development in China. Studies on screening of lung cancer, hepatocellular carcinoma (HCC), colorectal cancer, gastric cancer, esophageal cancer, and multiple cancers (pan-cancer screening) are reviewed and summarized. Liquid biopsy techniques detecting novel markers show great potential in the early screening of cancers, but still face challenges in sensitivity, specificity, productization, standardization, and cost-effectiveness. The emerging pan-cancer screening represents a direction of high-throughput and multiple cancer simultaneous screening, while it still needs optimization in detection performance and organ-specific recognition. Multi-omics integration analysis, artificial intelligence (AI)-assisted diagnosis, and large-scale prospective clinical studies will become important development steps in this field. Through a systematic review of the relevant literature, this paper describes in detail the development of new liquid biopsy technology, new progress in the field of cancer early screening, clinical application status, and future research direction. The review provides some useful insights into the future selection of early screening technology, the formulation of clinical research or trial protocols, and the balance between performance and cost.