Enumeration, classification and clinical application of circulating tumor cells in advanced gallbladder adenocarcinoma.

BACKGROUND: The relationship between circulating tumor cells (CTCs) and patients with advanced gallbladder adenocarcinoma (aGA) has been rarely studied. This article was to demonstrate the enumeration, classification, and clinical application of CTCs in patients with aGA. MATERIALS AND METHODS: Peripheral blood samples were collected and CTCs were detected using the CanPatrol(®) technique. T test, χ(2) test, Wilcoxon rank sum test or Kruskal-Wallis test, log-rank test and Cox regression analysis were performed to conduct statistical analysis. RESULTS: CTCs were detected at pre-treatment in 75.00% (27/36) of the patients. Both CTCs positive rate and CTCs enumeration at pre-treatment were significantly associated with clinicopathological parameters including Ca199 level (P = 0.014, P < 0.001 respectively), tumor differentiation (P = 0.007, P = 0.002 respectively), lymph infiltration (P = 0.010, P = 0.025 respectively), vascular infiltration (P = 0.007, P < 0.001 respectively), and distant metastasis (P = 0.015, P = 0.002 respectively). CTCs-positive patients had a significantly shorter OS (HR 0.335, 95% CI 0.165-0.678, P = 0.0023) and PFS (HR 0.364, 95% CI 0.179-0.739, P = 0.0024) than CTCs-negative patients. Mesenchymal CTCs enumeration was closely related to the chemotherapy response, and CTCs programmed cell death ligand-1 (PD-L1) was highly correlated with the immunotherapy response. Positive CTCs at pre-treatment was closely related to the poor OS (HR 0.089, 95% CI 0.020-0.399, P = 0.002) as well as distant metastasis (HR 0.159, 95% CI 0.041-0.610, P = 0.007), untreated with chemotherapy (HR 4.510, 95% CI 1.403-14.499, P = 0.011) and untreated with immunotherapy (HR 6.845, 95% CI 1.894-24.738, P = 0.003). CONCLUSION: Pretreatment-positive CTCs was closely related to the poor prognosis in patients with aGA. Monitoring the subtype and phenotype of CTCs may be one of the means to assess tumor treatment response.