Six genes found to connect pancreatic cancer with metabolic dysfunction

New research shows that the same genes are active in pancreatic cancer, obesity and diabetes, helping to explain why people with metabolic disease often face poorer cancer outcomes and pointing to future ways to predict recurrence and develop more targeted treatments.

In a study published in Cancer Medicine, researchers from the University of Birmingham, including experts supported by the National Institute for Health and Care Research (NIHR) Biomedical Research Centre: Birmingham, set out to test whether genes already linked to pancreatic cancer recurrence also behave differently in metabolic disease. Using large human and mouse genetic datasets, single cell analysis of pancreatic tumours, and laboratory testing of human tissue, they found consistent evidence that the same genes are active across both conditions.

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, characterised by late diagnosis, limited treatment options and a high risk of relapse, with around 80% of patients experiencing recurrence even after surgery. Obesity and type 2 diabetes are both known risk factors for PDAC, but the biological reasons for this link have not been fully understood.

We know that people with obesity or diabetes tend to have worse outcomes from pancreatic cancer, but the biological reasons have not been clear. Our study shows that the same genes and inflammatory pathways are active in both metabolic disease and pancreatic cancer, which helps explain this link and points to new opportunities for identifying high‑risk patients and developing more targeted treatments."

Dr. Animesh Acharjee, Associate Professor of Integrative Analytics and AI, University of Birmingham and senior author of the study

Key findings

Across all stages of the study, the researchers consistently observed increased activity of six genes – ITGAM, PECAM1, CCL5, STAT1, STAT2 and CD44 – previously associated with pancreatic cancer recurrence. These genes drive inflammatory and immune pathways and appear to form a shared biological link between metabolic disease and pancreatic cancer.

The study also identified a specific immune cell population inside pancreatic tumours where these pathways are particularly active, suggesting that inflammation linked to obesity or diabetes may help create conditions that support tumour growth and recurrence.

Piecing together the biological link

 To investigate shared biological mechanisms between pancreatic cancer and metabolic disease, the team used an integrative, multi‑stage approach that combined large‑scale analysis of human and mouse genetic data with detailed tumour‑level and laboratory validation.

First, they analysed publicly available genetic datasets from humans and mice to examine how key pancreatic cancer‑associated genes behave in healthy individuals compared with those with obesity, allowing them to identify consistent patterns across species.

They then analysed single‑cell data from human pancreatic tumours to examine activity within the tumour microenvironment. This revealed a specific group of immune cells showing high levels of inflammatory activity linked to both metabolic dysfunction and cancer progression.

Finally, the researchers validated their key findings in human tissue samples in the laboratory, confirming that several of the same genes were more active in obesity‑associated contexts.

Professor Simon Jones, Professor in Musculoskeletal Ageing at the University of Birmingham and Theme Lead for the NIHR Biomedical Research Centre: Birmingham Sarcopenia and Multimorbidity research theme, added:

"This study highlights how chronic inflammation and metabolic dysfunction can intersect with cancer biology. Understanding these shared mechanisms is essential if we are to improve outcomes for patients who are living with multiple long‑term conditions alongside cancer."

This study was funded by the Medical Research Council and Arthritis UK, and was delivered through the NIHR Biomedical Research Centre: Birmingham.