Clinical significance of circulating tumor cells and tumor markers in the diagnosis of lung cancer

Abstract

Background: Lung cancer has the highest fatality rate of all cancer types. To improve patients' survival and life quality, it is therefore very important to screen for and detect it at an early stage.

Methods: A negative enrichment-fluorescence in situ hybridization (NE-FISH) approach was used to detect circulating tumor cells (CTCs) in lung cancer patients, and levels of lung cancer-associated serum markers were also measured in the peripheral blood of these same patients. The correlation between CTCs, serum cancer markers (carcinoembryonic antigen [CEA], CA 125, CYFRA 21-1, and SCC), and clinicopathological characteristics was then investigated. Moreover, the potential clinical use of the combination of CTCs and tumor markers for the diagnosis of lung cancer, especially at early stages, was also explored.

Results: CTC frequencies in lung cancer patients were significantly higher than in healthy control volunteers or patients with benign lung disease, and the area under the receiver operating characteristics curve for the control group was 0.846 (95% CI 0.796-0.887, P < 0.001). The rate of CTC positivity in lung cancer patients was 68.29% when the CTC cutoff value was 2, and the sensitivity of this means of lung cancer detection rose to 82.93% by combining CTC-based detection with measurements of serum tumor markers. Similarly, the diagnostic sensitivity of this approach in early-stage lung cancer patients (I-II) was improved from 63.93% to 78.69%. Detection of CTCs can thus assist with the identification of benign and malignant pulmonary nodules.

Conclusions: It is potentially helpful and effective to employ a combination of CTCs and serum tumor markers for the clinical diagnosis of lung cancer.

Keywords: NE-FISH; circulating tumor cells; lung cancer; tumor markers.

Figure 1

Identification of CTCs by NE‐FISH. CEP, centromere probe; CTCs, circulating tumor cells; NE‐FISH, negative enrichment‐fluorescence in situ hybridization; WBC, white blood cells

Figure 2

CTC counts in patients and controls. A, Distribution of CTCs in controls and lung cancer. B, ROC curves used for determine the cutoff value for CTCs. C, Distribution of CTCs in patients with different pathological stage. CTCs, circulating tumor cells; ROC, receiver operating characteristics curve

Figure 3

CT scans of the lung cancer patients. A, B, 1.3‐cm ground glass nodule was present in the left upper lobe of the lung. C, D, 1.0‐cm ground glass nodule was present in the right middle lobe of the lung

Figure 4

Serum levels of CEA, CA 125, CYFRA 21‐1, and SCC in control and lung cancer (box plot with median, 10, 25, 75, and 90 centiles). CEA, carcinoembryonic antigen

Figure 5

Comparison between ROC curves in different diagnostic methods. A, Comparison of CTC, CEA, CA 125, CYFRA 21‐1, and SCC detection in 123 of lung cancer patients and 59 donors in control group. B, Comparison of CTC, CEA, CA 125, CYFRA 21‐1, and SCC detection in 61 of lung cancer patients with early stage and 59 donors in control group. C, Comparison among CTC, tumor markers (CEA, CA 125, CYFRA 21‐1, and SCC), and their combination detection in 123 of lung cancer patients and 59 donors in control group. D, Comparison among CTC, tumor markers (CEA, CA 125, CYFRA 21‐1, and SCC), and their combination detection in 61 of lung cancer patients with early stage and 59 donors in control group. ***P < 0.001; **P < 0.01. CEA, carcinoembryonic antigen; CTC, circulating tumor cell