Introduction: Lung cancer is a leading cause of death in patients with cancer. Early diagnosis is crucial to improve the prognosis of patients with lung cancer. Plasma circulating cell-free DNA (cfDNA) contains comprehensive genetic and epigenetic information from tissues throughout the body, suggesting that early detection of lung cancer can be done non-invasively, conveniently, and cost-effectively using high-sensitivity techniques such as sequencing.
Areas covered: In this review, we summarize the latest technological innovations, coupled with next-generation sequencing (NGS), regarding genomic alterations, methylation, and fragmentomic features of cfDNA for the early detection of lung cancer, as well as their clinical advances. Additionally, we discuss the suitability of study designs for diagnostic accuracy evaluation for different target populations and clinical questions.
Expert opinion: Currently, cfDNA-based early screening and diagnosis of lung cancer faces many challenges, such as unsatisfactory performance, lack of quality control standards, and poor repeatability. However, the progress of several large prospective studies employing epigenetic features has shown promising predictive performance, which has inspired cfDNA sequencing for future clinical applications. Furthermore, the development of multi-omics markers for lung cancer, including genome-wide methylation and fragmentomics, is expected to play an increasingly important role in the future.
Keywords: Circulating cell-free DNA; fragmentomics; lung cancer; methylation; screening and diagnosis.