Researchers at the University of Birmingham have found that the same genes are active in pancreatic cancer, obesity, and diabetes. Their findings, published in Cancer Medicine, could finally provide an explanation to why metabolic disease is a major risk factor for pancreatic cancer.
“We know that people with obesity or diabetes tend to have worse outcomes from pancreatic cancer, but the biological reasons have not been clear,” says Animesh Acharjee, PhD, associate professor of integrative analytics and AI at the University of Birmingham and senior author of the study. “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.”
Treatment options are currently limited for patients diagnosed with pancreatic cancer, a form of cancer that is often diagnosed at advanced stages. Only about 15% of patients are eligible for surgery, and about 80% of them relapse after treatment.
Previously, the researchers had identified a series of genes that were consistently altered in metastatic pancreatic tumors. In the current study, they examined whether these same genes also play a role in metabolic disorders such as obesity and diabetes, which are increasingly recognized as risk factors for pancreatic cancer.
First, the team analyzed genetic data from publicly available datasets to study how six key drivers of pancreatic cancer behave in healthy individuals compared to people with obesity. These included the ITGAM, PECAM1, CCL5, STAT1, STAT2, and CD44 genes, which are involved in inflammation, immune cell recruitment, and lipid metabolism processes. All six genes were found to be upregulated in individuals with obesity.
Single-cell RNA sequencing of patient tumor samples revealed that a subset of immune cells, including macrophages and monocytes found within the tumor microenvironment, expressed these core six genes at higher levels than other cells. This discovery suggests this group of cells may be key drivers of tumor progression and recurrence and a potential therapeutic target for the development of targeted therapies.
Taken together, these findings indicate that immune and inflammatory pathways that drive metabolic disease also play a major role in pancreatic cancer, where they could be involved in immune evasion and recurrence after surgery. Future work will investigate whether modulating the activity of these genes could reduce the chronic inflammation and immune dysregulation that drive the recurrence of pancreatic cancer to improve the success rate of this procedure. Targeting these pathways could offer new therapeutic strategies to manage pancreatic cancer, especially in patients with underlying metabolic conditions.
“This study highlights how chronic inflammation and metabolic dysfunction can intersect with cancer biology,” says Simon Jones, PhD, professor in musculoskeletal aging at the University of Birmingham and team lead for the NIHR Biomedical Research Centre. “Understanding these shared mechanisms is essential if we are to improve outcomes for patients who are living with multiple long‑term conditions alongside cancer.”
The post Pancreatic Cancer Shares Genetic Drivers with Obesity and Diabetes appeared first on Inside Precision Medicine.