Prognostic and Diagnostic Values of Circulating Tumor Cells and Tumor Markers for Lung Cancer.

BACKGROUND: Circulating tumor cells (CTCs) and tumor markers (TMs) are two kinds of diagnostic and prognostic markers for lung cancer. CTCs detect tumor cells, while TMs detect molecules in peripheral blood. This study aimed to investigate which marker is a better choice for the diagnosis and prognostication of lung cancer. METHODS: The diagnostic values were compared by generating receiver operating characteristic (ROC) curves and performing logistic regression analyses. The prognostic values were compared by generating Kaplan-Meier curves of CTCs, TMs, and clinical characteristics. RESULTS: The ROC curve analysis showed that CEA had the highest AUC (area under curve) among the TMs, while CTCs had a higher AUC than any of the TMs. Logistic regression analysis indicated that gender, smoking status, CTCs, and CA15-3 were involved in lung cancer prediction. The Kaplan-Meier curves showed that smoking status, pleural invasion, lymph node infiltration, and stage I - II disease were related to poor prognosis. Patients with CTCs or CA125 positivity also had a poor prognosis. CONCLUSIONS: Our data indicate that CTCs are a better choice than TMs for the diagnosis and prognostication of lung cancer.

Blocking podoplanin inhibits platelet activation and decreases cancer-associated venous thrombosis.

BACKGROUND: Patients with cancer are at a high risk of venous thromboembolism (VTE), studies have shown that high expression of podoplanin (PDPN) in tumors is associated with increased risk of VTE. METHODS: Two human malignant cell lines (NCI-H226 and C8161) expressing high levels of PDPN were selected to explore the role of platelet in cancer-associated venous thrombosis in vitro and in vivo. Immunohistochemical staining using anti-PDPN antibody was performed in the pulmonary carcinoma patients. RESULTS: Both NCI-H226 and C8161 cells expressing high PDPN triggered platelet activation via CLEC-2 in vitro, which was abrogated by an anti-PDPN antibody SZ-168. Furthermore, the in vivo study revealed that injection of CHO-PDPN or C8161 in two mouse model of venous thrombosis activated platelets, increased platelet counts and enhanced thrombosis. More importantly, PDPN-enhanced thrombosis was reduced in mice treated with SZ168. A total of 63.3% tumor specimens stained positive for PDPN. High PDPN expression was associated with an increased risk of VTE and poor prognosis. CONCLUSIONS: PDPN expression in tumors induced platelet activation and was related to a high risk of VTE via platelet activation. SZ168 inhibited PDPN-induced platelet activation in vitro and decreased the incidence of VTE in mice.

The Clinical Significance of Abnormal Tim-3 Expression on NK Cells from Patients with Gastric Cancer.

AIM: To investigate the clinical significance of Tim-3 (T-cell immunoglobulin- and mucin-domain-containing molecule 3) expression in natural killer (NK) cells from patients with gastric cancer. MATERIALS AND METHODS: Sixty-two patients with gastric cancer and 32 healthy controls were recruited for this study. Tim-3 expression in peripheral blood samples was analyzed using flow cytometry. The expression pattern of Tim-3 on NK cells was also confirmed using a gastric cancer-bearing mouse model. To further investigate the mechanisms that regulate Tim-3 expression, T-bet(-/-), Eomes(-/-), and Eomes/T-bet double knockout mice were utilized. Additionally, we statistically analyzed the clinical significance of Tim-3 expression on NK cells. RESULTS: We found that the levels of Tim-3 in NK cells obtained from patients with gastric cancer were significantly higher than the levels in healthy controls. Clinical analyses showed that Tim-3 levels on NK cells were associated with advanced tumor stage. In a tumor-bearing mouse model, Tim-3 levels in NK cells increased with tumor growth, indicating that tumor progression could induce Tim-3 expression in NK cells. Finally, we report that T-bet is a key factor involved in regulating Tim-3 expression. CONCLUSION: Our data indicate that Tim-3 expression on NK cells is regulated by T-bet, and that Tim-3 levels correlate with advanced stages of gastric cancer.