Circulating Tumor Cell and Metabolites as Novel Biomarkers for Early-stage Lung Cancer Diagnosis

Background: Lung cancer is a malignant tumor that has the highest morbidity and mortality rate among all cancers. Early diagnosis of lung cancer is a key factor in reducing mortality and improving prognosis. Methods: In this study, we performed CTC next-generation sequencing (NGS) in early-stage lung cancer patients to identify lung cancer-related gene mutations. Meanwhile, a serum liquid chromatography-tandem mass spectrometry (LC-MS) untargeted metabolomics analysis was performed in the CTC-positive patients, and the early diagnostic value of these assays in lung cancer was analyzed. Results: 62.5% (30/48) of lung cancer patients had ≥ 1 CTC. By CTC NGS, we found that > 50% of patients had 4 commonly mutated genes, namely, NOTCH1, IGF2, EGFR, and PTCH1. 47.37% (9/19) patients had ARIDH1 mutations. Additionally, 30 CTC-positive patients and 30 healthy volunteers were subjected to LC-MS untargeted metabolomics analysis. We found 100 different metabolites, and 10 different metabolites were identified through analysis, which may have potential clinical application value in the diagnosis of CTC-positive early-stage lung cancer (AUC > 0.9). Conclusions: Our results indicate that NGS of CTC and metabolomics may provide new tumor markers for the early diagnosis of lung cancer. This possibility requires more in-depth large-sample research for verification.