Methylation analyses in liquid biopsy

Lung cancer is the second most common cancer in the United States, and is the leading cause of cancer-related deaths worldwide. Patients diagnosed at an early stage have the best chance for survival. Unfortunately, only one third of patients with non-small cell lung cancer (NSCLC), which represents more than 80% of lung cancer cases, are diagnosed with localized, potentially curable disease (1). Screening using low-dose computed tomography (LDCT) has recently been shown to improve the early detection of lung cancer –60% of the cases diagnosed at stage I—and reduce cancer mortality by 20% compared to chest radiography (2). Although very promising, LDCT scanning identifies a high number of nodules that prompt further, invasive testing but do not result in a lung cancer diagnosis (2), detects many lung cancers that seem to be indolent (3), and remains a costly screening method to implement. Changing eligibility criteria for LDCT screening, from heavy smokers (at least 30 pack-years, current smokers or with no more than 15 years since quitting) aged 55 to 80 years, to a risk-based selection of ever-smokers aged 50 to 80 years, has been shown to improve screening effectiveness and efficiency (4). In addition, the systematic computational extraction, mining and interpretation of imaging features found in CT scans of lung cancer patients has led to the development of a prognostic signature (5,6). Radiomics-based biomarkers are now also being evaluated for performance in risk stratification of lung cancer patients diagnosed by LDCT to facilitate individualized patient management (7). Surgery is the main treatment for stage I NSCLC, but some patients with stage IB receive adjuvant chemotherapy to reduce the risk of disease recurrence. Still, 30% of patients experience relapse and die of their disease (8). Developing new markers for the early detection, prognosis and monitoring of lung cancer is therefore urgently needed to increase the efficacy of screening and reduce disease mortality