Utility of Liquid Biopsy (CTCs) after Liver Transplantation in Cirrhotic Patients with Hepatocarcinoma
Pablo p Ramirez Romero1, LF L Saenz Mateos2, Pedro p Cascales Campos1, Rocio MR Gonzalez Sanchez1, E E Llácer-Millán1, M MI Sanchez-Lorencio3, E E Díaz-Rubio4, Luis Martinez Insfran1, V V De La Orden5, B B Mediero-Valeros5, J JL Navarro6, B B Revilla Nuin7, A A Baroja-Mazo7, JA JA Noguera-Velazco3, Jesus J De La Peña8, David D Ferreras1, Jose Antonio JA Pons9, Francisco F Sanchez Bueno1, Ricardo R Robles Campos1, Pascual P Parrilla Paricio1.
1 Liver Transplant Unit, Department of Surgery., Clinical University Hospital Virgen de la Arrixaca, El Palmar, Spain; 2 Clinical Analysis Department, Navarre Hospital Complex, Pamplona, Spain; 3Clinical Analysis Department, Clinical University Hospital Virgen de la Arrixaca-IMIB, El Palmar, Spain; 4Medical Oncology Department, Clinical Hospital San Carlos, Madrid, Spain; 5CTC Unit, Medical Oncology Department, Clinical Hospital San Carlos, Madrid, Spain; 6 Department of Nuclear Medicine, Clinical University Hospital Virgen de la Arrixaca, El Palmar, Spain; 7Biomedical Research Institute of Murcia (IMIB-Arrixaca-UMU), Clinical University Hospital Virgen de la Arrixaca, El Palmar, Spain; 8Department of Pathology, Clinical University Hospital Virgen de la Arrixaca, El Palmar, Spain; 9Department of Hepatology, Clinical University Hospital Virgen de la Arrixaca, El Palmar, Spain
Introduction: New markers associated with angiogenesis and tumor metastasis, such as circulating tumor cells (CTCs), are opening up new avenues in cancer management from the laboratory.
The Aim of this work is to determine the number of CTCs in patients included in waiting list for liver transplantation of hepatocellular carcinoma and to study its possible association with the alpha fetoprotein tumor marker (AFP) and with clinical variables such as number of tumors, presence of tumor vascular invasion, waiting list time, time from diagnosis and post-transplant tumor recurrence. In addition, we intend to compare the pre-transplant levels of CTCs with those obtained one month, six months, one year and two years after the transplant.
Materials and Methods: Peripheral blood of 36 patients suffering hepatocellular carcinoma once included in waiting list for liver transplant was obtained. 29 of them were transplanted, 27 of whom had blood extracted one month after the transplant, 19 of them after 6 months and one year after the transplant and 11 of them two years after the transplant.
In order to study the correlation between the concentration of CTCs and the concentration of AFP, number of tumors, time on waiting list and from diagnosis in the patients, the Rho Spearman test was used. The study of the association of the CTCs levels with vascular invasion and presence of post-transplant recurrence was conducted with Mann-Whitney U test. For the variation in the levels of CTCs before and after the transplant, the Wilcoxon (SPSS 15.0) test was used.
Results: The average concentration of CTCs in the 36 patients before transplant was 11.50 CTCs/10mL (RI=2.25-42). A statistically significant positive correlation was found between the pre-transplant levels of CTCs and the days on waiting list (Rho= 0,376 p=0,024). The CTCs were not correlated in a significant way with the AFP concentration, number of tumors and time since diagnosis. (p>0,05). Out of the 29 transplanted patients, 2 showed vascular invasion in liver. Differences in the levels of CTCs were found between the patients with and without vascular invasion (U=0,00 p=0,020), these being significantly higher in the patients with vascular invasion. However, no significant differences were found in the levels of CTCs of the patients with recurrence after transplantation (4 patients) as opposed to those who didn’t (U=42 p=0.611).
Conclusions: Our conclusion is that the levels of tumor cells in peripheral blood could be an unfavourable prognostic factor associated to longer waiting times and to the presence of vascular invasion by tumor with an increased risk of relapse and post-transplant metastasis. In addition, we can see how their levels decrease significantly after transplantation. However, it would be necessary to increase the number of patients in the study, as well as the follow-up time, in order to achieve greater clinical evidence for its utility.
