Lung cancer is the most common cause of cancer-related mortality worldwide. Early diagnosis and surgery may be one of the most important strategy for the treatment of lung cancer patients. However, the procedure of lung cancer diagnosis from initial suspicion to final confirmation is not efficient due to low sensitivity of current diagnostic methods and difficulties involved in tumor tissue biopsy in lung cancer compared to other cancer types. Therefore, we investigated the feasibility of liquid biopsy using circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) analysis for the better diagnosis of lung cancer.
In this study, we blindly analyzed both CTCs and ctDNA in the blood samples derived from 109 patients including histology-proven and clinically suspicious lung cancer patients to test the sensitivity of liquid biopsy methods. CTC analysis was done by CytoGen’s liquid biopsy platform, in which viable CTCs were isolated by size-based filtration with gravity and validated by immunostaining of EpCAM or CK, excluding CD45 positive cells and enumerated by CytoGen’s cell imaging software. Lung cancer diagnosis was predicted by a cut-off, 2 ≥ CTC in 5 ml peripheral blood. For ctDNA analysis, EDGC F-Can platform was used to analyze single nucleotide variations of very low variant allele frequencies by utilizing unique molecular indexes and a novel read error correction algorithm. For comparison, we also analyzed the levels of conventional tumor markers (CEA, cyfra21-1 and NSE) in the patient cohort.
Compared to the diagnostic sensitivities of conventional tumor markers (CEA 29%; cyfra21-1 41%; NSE 39%), both assays of CTCs and ctDNA showed higher diagnostic sensitivity in predicting primary lung cancer (CTCs 67%; ctDNA 83%). When the assays of CTCs and ctDNA were combined for the diagnosis, the sensitivity was increased up to 98%.
Collectively, this study suggests that combined CTCs and ctDNA assay would be useful for the diagnosis of primary lung cancer.
Cytogen, Inc., EDGC, Inc., Department of Medicine, Samsung Medical Center
Has not received any funding
All authors have declared no conflicts of interest.