Proteômica dos efetores da recorrência do carcinoma hepatocelular após transplante hepático

Abstract

world, ranking sixth in terms of incidence and fourth, when analyzing mortality data. Liver transplantation has become the standard treatment for early-stage hepatocellular carcinomas (HCCs). This modality proves to be advantageous, because it treats not only HCC, but also the underlying cirrhosis, which is the main risk factor for the development of new tumors. Although it is the best treatment, the number of patients on the lists is greater than the available organs, requiring a selection of patients who will benefit from transplantation. Even with a careful selection of patients for transplantation, the recurrence after liver transplantation is around 8 to 20%. Therefore, it is extremely important to try to identify a molecular profile and correlate with the recurrence of this neoplasia. Patients and Methods: Samples were collected from 49 formalin fixed and paraffin embedded (FFPE) tissues of patients submitted to liver transplantation between 2011 and 2018. The specimens were 07 FFPE liver grafts tissues, 01 FFPE sample of tumor and 01 FFPE sample of the cirrhotic liver from each subject of 08 HCC relapsed patients, 01 FFPE HCC samples and 01 FFPE samples of the cirrhotic livers from each subject of 13 patients who did not recur. A dewaxing and protein digestion protocol was carried out. The samples were analyzed by a Dionex Ultimate 3000 RLSCnano-UPLC chromatographic system coupled to an LTQOrbitrap Elite mass spectrometer (Thermo Fisher Scientific). Results and discussion: Nine highly relevant proteins were found in the recurrent tumor scenario: PHGDH, SHMT2, ARF4, SQSTM1, FLNA, HSPD1, MYH9, MARCKS, TIMM-13. The main biological processes involved in this scenario were oxidative stress, cell division / adhesion / motility, mitochondrial metabolism. 15 highly relevant proteins were found in the cirrhotic liver scenario of patients that relapsed after liver transplantation: FLNA, HSPD1, FN1, HDGF, CANX, GDA, COL4A2, EML4, CALR, SERPINA1, GWL / MASTL, QDPR, B2M, TAGLN SOD1. The main biological processes involved in this scenario were amino acid metabolism, cell adhesion / division / motility, oxidative stress, cell signaling, immune response. Conclusion: There are differences between the protein profile found in the scenario of hepatocellular carcinomas that relapsed after liver transplantation and those that did not relapse and they are mainly related to the processes of cell division/adhesion/motility. There are also differences between the scenario of the cirrhotic liver of patients with recurrent tumor and those of patients whose tumors did not recur, being mainly related to the processes of cell division/adhesion/motility, followed by changes in cell metabolism and in the amino acid regime.