Utilidad de la biopsia líquida y otros marcadores tumorales en el trasplante hepático por hepatocarcinoma

Resum

Hepatocellular carcinoma (HCC) accounts for 80-90% of primary liver cancers. The only potentially curative options are resection and liver transplantation. It is known that the metastatic spread of a localized carcinoma occurs at an early stage through the dissemination of circulating tumor cells (CTCs). These cells provide us a real-time liquid biopsy, which can be useful for staging the cancer and predicting its evolution. In addition, the microenvironment of the tumor is made up of a series of molecules that play an important role in the proliferation and survival of cells, as well as in angiogenesis and metastasis. The aim of this study was to analyze the pre-transplant and post-liver transplant concentrations of peripheral's blood CTCs, together with other biomarkers, in patients with HCC, and establish their relationship with the progression of the disease and with the survival after liver transplant. For this purpose, an observational analytical study of dynamic prospective cohorts has been developed, in which the data obtained from a cohort of liver transplant patients with the diagnosis of HCC, within the Milan criteria, was analyzed between September 2014 and October 2017, within the Hepatic Transplant program of the Clinical University Virgen de la Arrixaca Hospital (Murcia). After analyzing the results, we found that the best CTCs detection method was the Isoflux¿ system. The levels of CTCs decreased after transplantation and, high CTCs pre-transplant levels, were associated with poor prognosis biochemical and clinical parameters (bilirubin, CRP, vascular invasion, number of tumors and time on waiting list) and a lower disease free survival rate after transplant. Alpha-fetoprotein (AFP), metalloprotease 1 (MMP-1), osteopontin (OPN) and interleukin 8 (IL-8) levels decreased after surgery. However, they increased in those patients with tumor recurrence. In addition, a trend towards lower survival without recurrence after transplantation was observed in those patients with higher AFP and MMP-1 pre-transplant levels. Therefore, our results show that CTC levels decrease after curative surgery and its determination may have a useful clinical implication to predicting the evolution of HCC after transplantation. AFP, MMP-1, OPN and IL-8 levels could also be useful for monitoring response to treatment and recurrence after curative surgery in HCC.