Overcoming Obstacles in Pathological Diagnosis of Pulmonary Nodules through Circulating Tumor Cell Enrichment

Abstract With the popularity of low‐dose computed tomography (LDCT) in clinical examination of the lung, the prevalence of pulmonary nodules has significantly increased, thus significantly improving the early diagnosis of lung cancer, but also potentially contributing to overtreatment. This study aims to develop a noninvasive method to assist in diagnosing the pulmonary nodules. To do so, 3798 patients are recruited from the Department of Thoracic Surgery at Shanghai Pulmonary Hospital and peripheral blood samples are collected from them before surgery. From these samples, circulating tumor cells (CTC) are isolated using folate receptor (FR) positivity, and then enriched and analyzed in relation to cancer gene expression, stage, and level of invasion. The average CTC concentration of patients with lung disease is 11.97 functional unit (FU) in a 3 mL sample of blood. FR‐positive CTC levels correlate with the expression of lung cancer driver genes tumor‐node‐matastasis (TNM) stage, and pleura invasion. The sensitivity of CTC levels to lung cancer diagnosis is 87.05%. Results from this study demonstrate that the determination of FR‐positive CTC concentration is a convenient and time‐saving strategy to improve the pathological diagnosis of pulmonary nodules.