A new study has revealed that low levels of CTDNEP1 may drive early and deadly pancreatic tumours, highlighting its role as a tumour suppressor. 

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and begins in the cells lining the pancreatic duct. Accounting for more than 90% of all pancreatic cancers, PDAC is extremely difficult to treat and has a very high mortality rate.  

In search of potential treatments, Mayuka Nii, a second-year doctoral student, and Professor Tadayoshi Hayata from the Faculty of Pharmaceutical Sciences at Tokyo University of Science, Japan, turned their attention to the gene CTD nuclear membrane phosphatase 1 (CTDNEP1).  

This gene encodes a phosphatase involved in several cellular pathways and is known to be involved in medulloblastoma, a paediatric brain tumour. 

“PDAC is one of the most difficult cancers to treat and has a very high mortality rate. To find new treatments, it is important to identify genes involved in cancer progression. Our research points to CTDNEP1 as a possible tumour-suppressing gene that could help slow the cancer,” said Professor Hayata. 

CTDNEP1’s role in survival rates

To explore this, the researchers analysed data from The Cancer Genome Atlas (TCGA) and the Pan-Cancer Atlas, which include genetic and clinical information from 184 patients with PDAC. They also used TIMER2.0 (Tumor IMmube Estimation Resource) and UALCAN (the University of ALabama at Birmingham CANcer data analysis Portal), two web resources for studying cancer-related genes and immune cell infiltration. Using these sources, the team examined CTDNEP1’s relationship with patient survival, its biological functions, and its interaction with the tumour’s immune environment. 

Their findings revealed that CTDNEP1 levels were significantly lower in PDAC tissue compared to healthy tissue, especially in the early stages of the disease. When CTDNEP1 was low, tumours were more likely to carry harmful mutations in key cancer-related genes such as KRAS and TP53. Patients with low CTDNEP1 expression had significantly poorer survival rates, particularly those diagnosed with stage II cancer. 

CTDNEP1 was also found to influence the tumour microenvironment. They found that low CTDNEP1 expression creates an environment that helps tumours evade the immune system. Low expression was associated with chronic inflammation, which can damage surrounding tissues and promote tumour growth. In contrast, tumours with high CTDNEP1 expression showed stronger metabolic and mitochondrial activity and had higher infiltration of immune cells, suggesting a more active and less suppressed immune environment. 

The research team is now conducting in vitro and in vivo investigations to understand how CTDNEP1 affects pancreatic cancer cell proliferation, metastasis, and immune interactions. By identifying the regulatory mechanisms that control CTDNEP1 expression, the researchers aim to uncover new therapeutic targets.