Periodic Reporting for period 1 - GENIAL (Understanding Gene ENvironment Interaction in ALcohol-related hepatocellular carcinoma)
Reporting period: 2023-01-01 to 2024-06-30
The GENIAL project addresses a critical European health challenge: alcohol-related hepatocellular carcinoma (ALD-HCC), the most common cause of liver cancer. This disease, directly caused by alcohol consumption, significantly burdens public health systems and patient quality of life as it is often diagnosed late when treatment options are limited.
GENIAL's core objective is to deepen our understanding of ALD-HCC development mechanisms, focusing specifically on the interplay between genetic predisposition and environmental factors, By examining this gene-environment interaction, the project aims to uncover why some individuals who consume alcohol develop ALD-HCC while others do not and try to uncover potential therapeutic targets.While GENIAL's primary focus is on understanding mechanisms, its findings have the potential to impact prevention strategies and early detection through improved risk stratification.
Given that ALD-HCC is the most common cause of liver cancer, the third leading cause of cancer death globally, GENIAL's potential impact is substantial. By integrating diverse data types with AI technologies to study gene-environment interactions, GENIAL could provide crucial insights into ALD-HCC development, potentially benefiting thousands of patients across Europe. This aligns with EU Cancer Mission objectives to improve understanding of cancer mechanisms and risk factors, with implications for prevention and early detection strategies.
GENIAL's core objective is to deepen our understanding of ALD-HCC development mechanisms, focusing specifically on the interplay between genetic predisposition and environmental factors, By examining this gene-environment interaction, the project aims to uncover why some individuals who consume alcohol develop ALD-HCC while others do not and try to uncover potential therapeutic targets.While GENIAL's primary focus is on understanding mechanisms, its findings have the potential to impact prevention strategies and early detection through improved risk stratification.
Given that ALD-HCC is the most common cause of liver cancer, the third leading cause of cancer death globally, GENIAL's potential impact is substantial. By integrating diverse data types with AI technologies to study gene-environment interactions, GENIAL could provide crucial insights into ALD-HCC development, potentially benefiting thousands of patients across Europe. This aligns with EU Cancer Mission objectives to improve understanding of cancer mechanisms and risk factors, with implications for prevention and early detection strategies.
During the first reporting period, GENIAL has made significant progress across all work packages (WP), laying a strong foundation for achieving its objectives.
In WP1, a crucial milestone was reached with the construction of an extensive patient dataset with and without ALD-HCC. While our initial patient inclusion goals have been met, the GENIAL consortium continues to actively recruit patient samples to enhance the statistical power of future analyses. The identification of novel common and rare variants predisposing to ALD-HCC is currently in progress, promising valuable insights into ALD-HCC development.
In WP2, we identified a neuroimmune hub that responds to body energy levels. This hub establishes an inter-organ communication route that controls endocrine function and liver metabolism, providing crucial insights into gene-environmental interactions influencing liver health. Additionally, multimodal datasets combining spatial metabolomics, transcriptomics, and single cell/nuclei sequencing from ALD-HCC patients are now prepared for comprehensive data integration. A novel method, "SCherlock," has been developed to identify robust cell markers from these complex datasets, enhancing our ability to characterize the cellular landscape of ALD-HCC.
In WP3, we established cohorts of patients followed prospectively (CIRRAL, CirVir, NASH-AVC, SERENA) have secured all necessary authorizations for participation in GENIAL and are currently under analysis. Adjoining biobanks, including constitutional DNA and liver biopsies, have received authorization for exploitation in the development of complex algorithms that integrate clinical, genetic and digital imaging data. Looking ahead, environmental questionnaires are scheduled for implementation in September 2024, while the creation of imaging biobanks is set to commence in 2025.
In WP1, a crucial milestone was reached with the construction of an extensive patient dataset with and without ALD-HCC. While our initial patient inclusion goals have been met, the GENIAL consortium continues to actively recruit patient samples to enhance the statistical power of future analyses. The identification of novel common and rare variants predisposing to ALD-HCC is currently in progress, promising valuable insights into ALD-HCC development.
In WP2, we identified a neuroimmune hub that responds to body energy levels. This hub establishes an inter-organ communication route that controls endocrine function and liver metabolism, providing crucial insights into gene-environmental interactions influencing liver health. Additionally, multimodal datasets combining spatial metabolomics, transcriptomics, and single cell/nuclei sequencing from ALD-HCC patients are now prepared for comprehensive data integration. A novel method, "SCherlock," has been developed to identify robust cell markers from these complex datasets, enhancing our ability to characterize the cellular landscape of ALD-HCC.
In WP3, we established cohorts of patients followed prospectively (CIRRAL, CirVir, NASH-AVC, SERENA) have secured all necessary authorizations for participation in GENIAL and are currently under analysis. Adjoining biobanks, including constitutional DNA and liver biopsies, have received authorization for exploitation in the development of complex algorithms that integrate clinical, genetic and digital imaging data. Looking ahead, environmental questionnaires are scheduled for implementation in September 2024, while the creation of imaging biobanks is set to commence in 2025.
GENIAL has already successfully constituted several databases related to genetic and clinical risk factors for ALD-HCC and developed new methods, yielding promising preliminary results. Our genetic study has exceeded patient recruitment targets, enhancing our ability to identify novel risk factors. Comprehensive analysis of multiple cohorts with patients followed prospectively, integrating diverse data types, will advance our predictive modeling capabilities. While these achievements position GENIAL at the forefront of liver cancer research, more effort is still needed to fully realize the project's ambitious goals.