循环肿瘤细胞和代谢物作为早期肺癌诊断的新型生物标志物

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

作者信息

Wan Lingling, Liu Qingyi, Liang Di, Guo Yongdong, Liu Guangjie, Ren Jinxia, He Yutong, Shan Baoen

机构信息

Cancer Institute, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, China.

Department of Thoracic Surgery, The Fourth Hospital of Hebei Medical University/The Tumor Hospital of Hebei Province, Shijiazhuang, China.

出版信息

Front Oncol. 2021 May 31;11:630672. doi: 10.3389/fonc.2021.630672. eCollection 2021.

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, , , , and . 47.37% (9/19) patients had 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.

背景

肺癌是所有癌症中发病率和死亡率最高的恶性肿瘤。肺癌的早期诊断是降低死亡率和改善预后的关键因素。

方法

在本研究中，我们对早期肺癌患者进行了循环肿瘤细胞（CTC）下一代测序（NGS）以鉴定肺癌相关基因突变。同时，对CTC阳性患者进行了血清液相色谱-串联质谱（LC-MS）非靶向代谢组学分析。以筛选早期肺癌的潜在诊断标志物。

结果

62.5%（30/48）的肺癌患者有≥1个CTC。通过CTC NGS，我们发现>50%的患者有4个常见突变基因，即、、和。47.37%（9/19）的患者有突变。此外，对30例CTC阳性患者和30名健康志愿者进行了LC-MS非靶向代谢组学分析。我们发现了100种不同的代谢物，经分析鉴定出10种不同的代谢物，它们可能在CTC阳性早期肺癌的诊断中具有潜在的临床应用价值（曲线下面积>0.9）。