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Dr Daniel Hughes and colleagues identify NUDT15 as a potential biomarker for pancreatic cancer recurrence following surgery.

Pancreatic cancer has very poor outcomes, with only 7% of patients surviving the disease for 5 years in the UK. If diagnosed early enough, while the disease is still localised, surgical resection offers the chance of cure. However, 2 in 3 patients undergoing surgery experience early disease recurrence, despite receiving post-operative chemotherapy (data from the ESPAC 4 trial). There is a clinical need to predict patients at a high risk of early disease relapse so that their treatments can be better tailored, for example, by giving chemotherapy before surgery, improving patient selection for surgery and altering the frequency of post-operative disease monitoring.

In a study published in Current Oncology, Cancer Research UK Clinical Fellow Dr Daniel Hughes (Department of Oncology and Oxford University Hospitals NHS Trust) working with Professor Eric O’Neill (Department of Oncology) and colleagues looked for new biomarkers that are predictive of pancreatic cancer recurrence following surgical resection. The team studied RNA sequencing data from 95 patients with pancreatic ductal adenocarcinoma in the Cancer Genome Atlas database. By comparing the data from patients with early disease recurrence to those without early recurrence, they identified 5 genes that were expressed at different levels in the two groups of patients. Of these, a gene called NUDT15 looked to be the most promising biomarker candidate.

To validate NUTD15 as a biomarker for early recurrence, the team studied NUDT15 levels in a cohort of 13 patients from Oxford. Patients with tumours that recurred early had a higher level of NUDT15 protein compared to patients whose disease did not recur within a year of surgery. This finding suggests there is potential for raised levels of NUDT15 to be used as a predictive biomarker for early recurrence. 

These results now need to be validated in a larger patient cohort. To enhance the potential for early risk stratification, the team also plan to investigate whether NUDT15 can be detected in biopsies collected by pre-operative endoscopic ultrasound, in addition to the tumour tissue collected during surgery used in this study.

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