Applying circulating tumor DNA methylation in the diagnosis of lung cancer

Lung cancer is the leading cause of cancer-related deaths worldwide. Low dose computed tomography (LDCT) is commonly used for disease screening, with identified candidate cancerous regions further diagnosed using tissue biopsy. However, existing techniques are all invasive and unavoidably cause multiple complications. In contrast, liquid biopsy is a noninvasive, ideal surrogate for tissue biopsy that can identify circulating tumor DNA (ctDNA) containing tumorigenic signatures. It has been successfully implemented to assist treatment decisions and disease outcome prediction. ctDNA methylation, a type of lipid biopsy that profiles critical epigenetic alterations occurring during carcinogenesis, has gained increasing attention. Indeed, aberrant ctDNA methylation occurs at early stages in lung malignancy and therefore can be used as an alternative for the early diagnosis of lung cancer. In this review, we give a brief synopsis of the biological basis and detecting techniques of ctDNA methylation. We then summarize the latest progress in use of ctDNA methylation as a diagnosis biomarker. Lastly, we discuss the major issues that limit application of ctDNA methylation in the clinic, and propose possible solutions to enhance its usage.