AUTHOR=Wan Lingling , Liu Qingyi , Liang Di , Guo Yongdong , Liu Guangjie , Ren Jinxia , He Yutong , Shan Baoen TITLE=Circulating Tumor Cell and Metabolites as Novel Biomarkers for Early-Stage Lung Cancer Diagnosis JOURNAL=Frontiers in Oncology VOLUME=11 YEAR=2021 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.630672 DOI=10.3389/fonc.2021.630672 ISSN=2234-943X ABSTRACT=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. To screen potential diagnostic markers for early lung cancer.

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.