Mutational differences between primary cancer tissue and circulating tumor cells in early-stage non-small cell lung cancer.

Background: Early-stage non-small cell lung cancer (NSCLC) has a high recurrence rate despite proper management, including curative surgery. Circulating tumor cells (CTCs) are believed to play a key role in the distant metastasis of lung cancer. Immunofluorescence imaging studies of CTCs have revealed that they are associated with the prognosis of NSCLC. However, the mutational profiling of CTCs from early-stage NSCLC has not been extensively explored. We hypothesized that CTCs could be detected by mutational analysis using panel sequencing and would have distinct mutations associated with distant metastasis compared to those of primary cancer tissue in early-stage NSCLC. Thus, this study examined the DNA from CTCs using targeted panel sequencing to identify mutations and compared them with mutations found in primary cancer tissue in patients with resectable early-stage NSCLC.

Methods: Overall, 45 patients with resectable NSCLC were prospectively enrolled from September to December 2023. Matched whole blood samples and primary cancer tissues were collected during curative surgery. Then, 405-gene targeted panel sequencing was performed on DNA from primary cancer tissues and CTCs.

Results: In this study, 37 patients (82%) had adenocarcinoma, and 30 (67%) were classified as having pathologic stage 1 disease. Mutated genes were detected in all (100%) and 31 patients (69%) for primary cancer tissue and CTCs from panel sequencing, respectively. The partial concordance rate of mutations between primary cancer tissue and CTCs was 17.8%, with the top 10 mutated genes differing significantly. Among primary cancer tissue samples, mutated genes differed by stage and histologic type; these findings were not observed in CTCs. CTCs predominantly displayed mutations in tumor suppressor genes, whereas primary cancer tissues exhibited mutations in both oncogenes and tumor suppressor genes.

Conclusions: CTCs exhibited unique mutations, showing low concordance with mutations found in primary cancer tissue. CTCs may possess specific mutations independent from those of primary cancer tissue in early-stage NSCLC.