HMN 2026: How Potential tumor-suppressing gene is identified in pancreatic cancer

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.

According to the Global Cancer Observatory 2022 report, pancreatic cancer is the sixth most common cancer in Japan, with over 47,000 new cases and more than 40,000 deaths, making it the fourth leading cause of cancer-related mortality in the country.

Exploring the role of CTDNEP1 in cancer

In search of potential treatments, Ms. Mayuka Nii, a second-year doctoral student, and Professor Tadayoshi Hayata from the Faculty of Pharmaceutical Sciences at Tokyo University of Science, Japan, have 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 pediatric brain tumor.

Previously, the researchers had found that CTDNEP1 plays a suppressive role in osteoclast cell differentiation, which are cells involved in the breakdown and removal of old or damaged bone tissue. Now, with the results of their study, researchers believe that this gene may also play a protective role in pancreatic cancer and could contribute to its early detection.

The study is published in the journal Cancer Genomics & Proteomics.

“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 tumor-suppressing gene that could help slow the cancer,” says Prof. Hayata.

Key findings from genetic analysis

To explore this, the researchers analyzed 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 tumor’s immune environment.

Their findings reveal that CTDNEP1 plays an important role in pancreatic cancer. CTDNEP1 levels were significantly lower in PDAC tissue compared to healthy tissue, especially in the early stages of the disease. When CTDNEP1 was low, tumors 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 tumor microenvironment. They found that low CTDNEP1 expression creates an environment that helps tumors evade the immune system. Low expression was associated with chronic inflammation, which can damage surrounding tissues and promote tumor growth. In contrast, tumors 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.

Implications for early detection and treatment

“These results suggest that low CTDNEP1 expression occurs early in pancreatic cancer and may play a role in disease progression and malignancy,” explains Prof. Hayata.

This means CTDNEP1 could help in the early detection of pancreatic cancer, serve as a prognostic indicator for predicting disease severity, and potentially act as a therapeutic target, where modulating its activity might help slow or stop tumor growth.

“Personally, I have several acquaintances who died very young from pancreatic cancer. Hence, I undertook this research and it is my mission and personal desire as a researcher to translate this research into medical care,” shares Prof. Hayata.

Next steps and future research directions

Building on these discoveries, 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. Although the clinical significance of CTDNEP1 is still emerging, its potential role in early detection and disease modulation makes it a compelling candidate for future pancreatic cancer treatments.

While these findings are data-driven, they offer a promising starting point, which may ultimately lead to new and effective strategies against this disease.

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