Background: A growing body of research indicates that the monitoring of circulating tumor cells (CTCs) may have great significance to the diagnosis of malignant tumors, assessment of condition, selection of treatment methods, and evaluation of prognosis and has a broad range of potential applications. However, the value of CTCs with different phenotypes in the diagnosis of hepatocellular carcinoma (HCC) and assessment of patient condition remains unclear.
Methods: We collected 5 ml of peripheral blood from 176 patients who were found to have space-occupying lesions in the liver via B-ultrasound diagnosis at Zhujiang Hospital affiliated with Southern Medical University between August 2015 and October 2017 and used CanPatrol™ CTCs assay technology to isolate and count CTCs with different phenotypes in the patients' peripheral blood. This allowed analysis of the value of CTCs with different phenotypes in the diagnosis of HCC and assessment of BCLC stage.
Results: We used CanPatrol™ CTCs assay technology to isolate different types of CTCs: epithelial CTCs (only stained for epithelial markers), mesenchymal CTCs (only stained for mesenchymal markers), mixed CTCs (stained for epithelial markers and mesenchymal markers), and total CTCs (all of the foregoing CTC phenotypes). Of 176 observed patients, 6 patients were finally diagnosed as other malignant tumor liver metastasis, 113 were diagnosed as having hepatocellular carcinoma, and 57 were diagnosed as having nonmalignant liver diseases. Furthermore, we intend to evaluate the diagnostic value of different phenotype CTCs count in discrimination between hepatocellular carcinoma and nonmalignant liver diseases. We found that CTCs of all types were significantly more numerous in the peripheral blood of the HCC group patients than in the NLD group patients (P < 0.05). Furthermore, of the different types of CTCs, total CTCs had the greatest diagnostic value (AUC 0.774; 95% CI, 0.704-0.834). A further discovery was that the AUC values for total CTCs, AFP, and a combined model (combined use of total CTCs and AFP) were 0.774 (95%CI, 0.704-0.834), 0.669 (95%CI, 0.587-0.750), and 0.821 (95%CI, 0.756-0.886). Late-stage HCC patients (BCLC stage B-C) had a higher peripheral blood mesenchymal CTC count than early-stage patients (BCLC stage 0-A) (median:1 vs 0), and mesenchymal CTCs ≥ 1 was the cut-off value for the diagnosis of BCLC stage in HCC patients (sensitivity: 66.67%, specificity: 59.46%, Youden index: 0.26).
Conclusions: Total CTCs are more effective than AFP in the diagnosis of HCC; combined use of total CTCs and AFP can enhance the sensitivity of HCC diagnosis.
Keywords: Circulating tumor cells (CTCs); Diagnostic value; Hepatocellular carcinoma (HCC); Nonmalignant liver diseases (NLD).