Yuan Cheng1, Lei Luo2, Juqiang Zhang2, Mantian Zhou2, Yujun Tang1, Guolin He1, Yishi Lu1, Zhong Wang3, MingXin Pan4. 1. Second Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China. 2. Department of Interventional Vascular Surgery, the Central Hospital of Zhuzhou City, Zhuzhou, 412000, Hunan, China. 3. 458th Hospital of PAL, Guangzhou, 510062, China. 4. Second Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, 510282, China. pmxwxy@sohu.com.
Abstract
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.
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.
Authors: Peter Ferenci; Michael Fried; Douglas Labrecque; J Bruix; M Sherman; M Omata; J Heathcote; T Piratsivuth; Mike Kew; Jesse A Otegbayo; S S Zheng; S Sarin; S Hamid; Salma Barakat Modawi; Wolfgang Fleig; Suliman Fedail; Alan Thomson; Aamir Khan; Peter Malfertheiner; George Lau; F J Carillo; Justus Krabshuis; Anton Le Mair Journal: J Gastrointestin Liver Dis Date: 2010-09 Impact factor: 2.008
Authors: Luciana Kikuchi; Claudia P Oliveira; Mario R Alvares-da-Silva; Claudia M Tani; Marcio A Diniz; Jose T Stefano; Aline L Chagas; Regiane S S M Alencar; Denise C P Vezozzo; Gilmar R Santos; Priscila B Campos; Venancio Af Alves; Vlad Ratziu; Flair J Carrilho Journal: Am J Clin Oncol Date: 2016-10 Impact factor: 2.339
Authors: Joseph C Ahn; Pai-Chi Teng; Pin-Jung Chen; Edwin Posadas; Hsian-Rong Tseng; Shelly C Lu; Ju Dong Yang Journal: Hepatology Date: 2021-01-18 Impact factor: 17.425
Authors: María Lola Espejo-Cruz; Sandra González-Rubio; Javier Zamora-Olaya; Víctor Amado-Torres; Rafael Alejandre; Marina Sánchez-Frías; Rubén Ciria; Manuel De la Mata; Manuel Rodríguez-Perálvarez; Gustavo Ferrín Journal: Int J Mol Sci Date: 2021-12-03 Impact factor: 5.923