Periodic Reporting for period 1 - easi-IPMN (Early Inflammatory Signatures of IPMN Progression)
Reporting period: 2024-05-01 to 2025-10-31
Pancreatic ductal adenocarcinoma is one of the most lethal cancers, largely because it is usually diagnosed at an advanced stage. Intraductal papillary mucinous neoplasms are common pancreatic cystic lesions that can precede invasive cancer and are increasingly detected through routine imaging. However, current clinical criteria used to decide whether to operate or to monitor patients are imprecise and rely mainly on radiological features. This leads to a high rate of unnecessary surgery, while a smaller proportion of patients still progress to cancer despite surveillance. There is therefore a clear need for biological markers that can better distinguish low-risk from high-risk lesions. The easi-IPMN project aimed to address this gap by evaluating whether inflammation-related molecular signals present within pancreatic tissue could be used to improve risk stratification of IPMN patients. Building on previous research linking inflammatory processes to pancreatic cancer initiation, the project sought to validate and refine a molecular signature that could support more accurate clinical decision-making and ultimately reduce both overtreatment and delayed intervention.
The project combined molecular profiling of patient tissue samples with computational analysis and translational assessment. A curated cohort of IPMN patients was assembled, and spatial gene expression analyses were performed on archived tissue samples to measure inflammatory gene programs while preserving tissue structure. These analyses showed that the inflammatory signature could be reliably detected in IPMN lesions and that higher expression levels were associated with more advanced disease stages. To facilitate future clinical application, the initial molecular signature was simplified by identifying a smaller set of genes that retained strong association with disease progression. Additional in situ analyses helped define the cellular context in which these signals arise. Initial validation at the protein level was initiated using methods compatible with routine pathology practice. In parallel, the project evaluated intellectual property, market needs, and regulatory requirements, resulting in a clear roadmap for further development of the diagnostic concept.
The easi-IPMN project provides proof that tissue-based inflammatory molecular signals can be used to improve the biological stratification of pancreatic precursor lesions. By complementing existing imaging-based criteria with molecular information, this approach opens new possibilities for more precise and individualized patient management. The work also demonstrates the feasibility of translating complex molecular data into formats compatible with standard diagnostic workflows. Beyond its immediate application to IPMN, the project establishes a general framework for integrating spatial molecular information into clinical diagnostics. Further validation and development will be required, but the results lay the groundwork for future diagnostic tools that may improve patient outcomes while reducing unnecessary medical interventions and associated healthcare costs.