Childhood liver oncology (c-LOG)
The Childhood Liver Oncology Group (c-LOG) is a research group that forms part of the Gastroenterology department of the HUGTP, it is also part of the CIBERehd. The cLOG is also supported by the SEHOP and the European SIOPEL group.
The cLOG research lines based are focussed on increasing the molecular knowledge of the underlying mechanisms responsible for hepatocarcinogenesis and tumour progression. We use the latest omics and sequencing technologies in order to identify diagnostic/prognostic biomarkers and key molecular pathways for improving the clinical management and treatment of children suffering of liver cancer.
- Project 1. Establishment of a collection of biological samples from liver cancer patients (National Biobank Registry ref. C.0000226).
To boost translational research into childhood liver cancer, we created the first national collection of biospecimens from these patients in 2010. Nowadays, we are collecting samples from about 70-80% of the total number of patients diagnosed with this disease in Spain (Fig. 1). Thanks to our participation in the H2020 ChiLTERN project, we are now also collecting samples from European paediatric patients with liver cancer enrolled in the first international clinical trial (PHITT).
Figure 1. Childhood Liver Cancer incidence in Spain (data obtained from the National Registry of liver tumors in children, RNTI-SEHOP), including hepatoblastoma (HB) and hepatocellular carcinoma (HCC), and the number of patients whose samples have been included in the collection.
Importantly, our group, in collaboration with six hospitals, also established a collection of plasma and germline DNA samples from adult patients with distinct liver diseases, including chronic hepatitis, cirrhosis and HCC.
- Project 2. New insights into hepatoblastoma (HB) through proteomic profiling.
We performed the first proteomic study in HB samples with the idea to complement the knowledge of this tumour and identify new prognostic biomarkers at the protein level, because they can be applied in current medical practice more easily. As a result, we identified three prognostic biomarkers that were highly complementary between them and had a significant association with event-free survival (patent submission).
Figure 2. Patient stratification on the basis of the 3-protein signature, resulting in the combination of three prognostic biomarkers (BMs). Left, Kaplan Meier curves of Event-free survival; Right, Immunohistochemistry pictures of the three biomarkers in two patients (top, patient with a good prognostic profile with no biomarkers altered; bottom, patient with a poor prognostic profile with all three biomarkers altered).
- Project 3. Study to prospectively validate the use of biomarkers in clinical practice.
We have identified several biomarkers that could be useful to improve the clinical management of childhood liver cancer. The present ongoing study, included in the European ChiLTERN project, aimed to examine the expression/presence of a panel of biomarkers, including gene mutations and gene and protein expression signatures, in diagnostic samples obtained from patients enrolled in the PHITT clinical trial.
- Project 4. Comprehensive molecular characterization of hepatoblastoma.
This ambitious project is carried out by integrating RNA-sequencing, genomic, epigenomic and transcriptomic data with the aim to increase the molecular knowledge of HB. Through this project, we have identified new hallmarks of HB, including an oncogenic chromosomal region, a therapeutic drug against a specific kinase that blocks tumour growth, and a new genomic classification with a strong prognostic impact.
- Project 6. Establishment of pre-clinical models of childhood liver cancer.
We are also interested in developing new translational models of childhood liver cancer based on the establishment of orthotopic Patient-Derived Xenografts (PDXs) and organoid cultures. To date, we have been able to establish innovative pre-clinical models of HB that are being deeply characterized.
Carolina Armengol, PhD
(+34) 93 554 30 72