Therefore, we have investigated further the potential of SHOX2 and two additional methylation markers, forkhead box L2 gene (FOXL2) and prostaglandin E receptor 4 gene (PTGER4), for use as a noninvasive, blood plasma–based diagnostic tool to differentiate patients with LC from healthy subjects and patients with nonmalignant disease of the lung. Here, SHOX2 is linked to laryngotracheoesophageal cleft.