Periodic Reporting for period 4 - ESCALON (European-Latin American network for the assessment of biomarkers to predict and diagnose hepatobiliary malignancies and characterization of risk factors for cancer development)
Reporting period: 2023-01-01 to 2023-12-31
Hepatobiliary malignancies represent a major cause of mortality globally and are uniquely aggressive in Latin America. The most common tumors are: hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA), and gallbladder cancer (GBC). The excess mortality of these tumors is accompanied by the lack of reliable screening methods and the complexity of diagnosis, which requires advanced imaging technology and difficult-to-access tissue. These barriers are amplified by poor accessibility present in resource-limited regions, all of which leads to tumors being diagnosed at advanced stages in which curative therapy is not an option. Our research project will lead to the discovery and utilization of biomarkers that can be applied worldwide for early diagnosis and detection of HCC, CCA and GBC. The major aim of the ESCALON project is to enable early diagnosis of hepatobiliary cancers for Latin American and European citizens, and to identify leads for risk identification and primary prevention measures for these tumors.
The ESCALON consortium started in January 2019, and ended in December 2023. One of the crucial parts of the project has been the identification of patients with hepatobiliary cancer in Latin America and Europe, and their participation in the project. During the course of the project, we have successfully established unique databases and biobanks of patients with hepatocellular carcinoma (HCC), cholangiocarcinoma (CCA) and gallbladder cancer (GBC). In addition, also patients at risk of developing cancer were asked to participate in the project, which led to the establishment of both cross-sectional as well as prospective cohorts of patients with risk factors for cancer development. More than 1500 patients are included in our biobanks, and detailed clinical information is available from all patients. These databases and biobanks are unique since standardized cohorts of Latin American patients with hepatobiliary cancers are rare, and they have proven to be extremely valuable for the studies that are focused on the identification of risk factors and diagnostic biomarkers for all three types of hepatobiliary cancers.
The ESCALON project determined the clinical characteristics patients of patients with HCC, CCA and GBC, as well as of patients that are considered to be at-risk of developing these cancers, such as cirrhotic patients (for HCC), primary sclerosing cholangitis patients (for CCA) and individuals with gallstones (for GBC). Important differences were noted between Latin American and European patients. Risk factors for HCC such as aflatoxin exposure, and co-infections with hepatitis D and hepatitis E have been determined.
The consortium has optimized and validated numerous assays for the HCC and GBC part of the project. These include the measurement of multiple immune markers, and tumor markers in serum, microRNAs, gene polymorphisms and markers in extracellular vesicles. Distinctive serum biomarker panels, including immune proteins and tumor-derived proteins, have been identified that distinguish HCC and GBC from their respective at-risk groups. These panels that could be used to screen for liver cancer in a simple and affordable manner. Importantly, it became evident that the etiology associated with the liver disease as well as the presence or absence of cirrhosis were important determinants of the biomarker panels. For CCA, several candidate biomarkers have been identified with high diagnostic capacity for the early diagnosis of CCA in patients with primary sclerosing cholangitis (PSC) compared to control groups. In addition, potential common protein biomarkers were investigated in serum extracellular vesicles for the diagnosis of the different types of CCA (independently of the risk factor associated). Analysis of risk factors as well as predictive and diagnostic blood biomarkers for the various cancers has been conducted. Differences between results of Latin American and European samples and data were an important aspect of the analysis.
Dissemination of the data generated by the ESCALON consortium takes place via the ESCALON website and social media accounts. On the ESCALON website (www.escalon.eu) an extensive list of scientific publications can be found that were published since the start of the project. These publications describe in detail the findings of the project. In addition, symposia and lectures for professionals, students and patients were organized, as well as scientific seminars with invited speakers on topics relevant for the objectives of ESCALON.
The ESCALON project determined the clinical characteristics patients of patients with HCC, CCA and GBC, as well as of patients that are considered to be at-risk of developing these cancers, such as cirrhotic patients (for HCC), primary sclerosing cholangitis patients (for CCA) and individuals with gallstones (for GBC). Important differences were noted between Latin American and European patients. Risk factors for HCC such as aflatoxin exposure, and co-infections with hepatitis D and hepatitis E have been determined.
The consortium has optimized and validated numerous assays for the HCC and GBC part of the project. These include the measurement of multiple immune markers, and tumor markers in serum, microRNAs, gene polymorphisms and markers in extracellular vesicles. Distinctive serum biomarker panels, including immune proteins and tumor-derived proteins, have been identified that distinguish HCC and GBC from their respective at-risk groups. These panels that could be used to screen for liver cancer in a simple and affordable manner. Importantly, it became evident that the etiology associated with the liver disease as well as the presence or absence of cirrhosis were important determinants of the biomarker panels. For CCA, several candidate biomarkers have been identified with high diagnostic capacity for the early diagnosis of CCA in patients with primary sclerosing cholangitis (PSC) compared to control groups. In addition, potential common protein biomarkers were investigated in serum extracellular vesicles for the diagnosis of the different types of CCA (independently of the risk factor associated). Analysis of risk factors as well as predictive and diagnostic blood biomarkers for the various cancers has been conducted. Differences between results of Latin American and European samples and data were an important aspect of the analysis.
Dissemination of the data generated by the ESCALON consortium takes place via the ESCALON website and social media accounts. On the ESCALON website (www.escalon.eu) an extensive list of scientific publications can be found that were published since the start of the project. These publications describe in detail the findings of the project. In addition, symposia and lectures for professionals, students and patients were organized, as well as scientific seminars with invited speakers on topics relevant for the objectives of ESCALON.
There is still an urgent need for new and reliable biomarkers in order to detect and diagnose hepatobiliary malignancies. In ESCALON we evaluate epidemiological and clinical data from populations at risk for developing hepatobiliary malignancies in Europe and South America in order to detect tumour development at an early stage and to improve diagnosis. Our multicentre international study conducted in Latin America and Europe was able to identify and validate protein-based and etiology-related logistic models with predictive, diagnostic, or prognostic capacities by combining two to four circulating protein biomarkers, moving a step forward into personalised medicine, particularly for HCC and CCA. Although validation in larger and more diverse patient cohorts will contribute to add additional support for the use of these markers in the clinical setting, the results obtained with samples from both continents are highly promising. These novel liquid biopsy tools may contribute to the development of easy and non-invasive markers for early-detection of HCC, easy and non-invasive diagnosis of sporadic CCAs, establishment of cost-effective surveillance programs for the early detection of CCA in high-risk populations (e.g. PSC), and prognostic stratification of patients with CCA, which, altogether, may increase the number of cases eligible for potentially curative options or to receive more successful treatments, thereby decreasing mortality. Also, for gallbladder carcinomas, the consortium was able to establish an impressive database and biobank with data from this rare tumor. The project was able to detect important differences in profiles of GBC patients and high-risk populations (GSD) to discover and propose diagnostic and prognostic biomarkers that could be used in large-scale studies and public policy development in high-risk countries, such as Chile, Bolivia, Peru, and Ecuador.