The Clinical Values of Circulating Tumor Cells and T Lymphocyte Subsets in Predicting a Prognosis of Lung Cancer.

Background: Lung cancer is the most lethal cancer in men and women. Recently, it has been reported that circu-lating tumor cells (CTCs) are sensitive and reliable biomarkers for tracing relapse and metastasis of cancer patients. Many studies also showed that immune cellular dysfunctions in lung cancer patients are major reasons for cancer development. In this study, we explored the clinical significance of CTCs and T lymphocyte subtypes in lung cancer patients.

Methods: A total of 92 patients with diagnosed lung cancer, including 23 squamous-cell carcinoma and 69 adenocarcinoma, were enrolled in this study. Another 10 patients with non-carcinoma nodules in their lungs were also recruited as a control group. Peripheral blood samples were drawn from the patients with lung cancer and from the control cases before the treatment. The identification of CTCs was carried out by a PatrolCTC detection method. The T lymphocyte subtypes were characterized by flow cytometry (FACS). Cytokines interleukin-2 (IL-2), interleukin-4 (IL-4), interleukin-17A (IL-17A), interleukin-10 (IL-10), and interferon  (IFN-) were detected by meso scale discovery (MSD) assay.

Results: Out of the enrolled patients, 69 (75%) patients with non-small cell lung cancer (NSCLC) were male and 23 (25 %) were female. Smoking and non-smoking history was 50% (46 cases) each. The case numbers for I - IV tumor-node-metastasis (TNM) stages were 23 (25.0%), 28 (30.4%), 16 (17.4%), and 25 (27.2%), respectively. The positive rates of the CTCs before treatment were 8.7% (2/23), 17.6% (5/28), 81.3% (13/16), and 100% (25/25) in stage I, II, III, and IV patients, respectively. Total CTCs, mixed CTCs, and mesenchymal CTCs (MCTCs) were strongly related to the progression-free survival (PFS) of the patients. In addition, total CTCs (≥ 6) and positive MCTCs also significantly correlated with recurrence and metastasis. The patients with high CTCs also had low levels of CD4, CD4/CD8 ratio, IL-2, and IFN. In contrast, IL-10 in high CTCs patients was significant elevated. These results indicate that the CTC numbers in lung cancer patients are an independent indicator for a worse PFS.

Conclusions: Higher total CTCs, mixed CTCs, and MCTCs in peripheral blood were significant biomarkers for predicting the prognosis of lung cancer patients. High CTCs also had a strong correlation with weak cellular immunity functions.