Renal cell carcinoma (RCC) is the most common form of kidney cancer, accounting for about 90% of kidney cancers. It develops when abnormal cells in the kidney's small tubules begin to grow uncontrollably. RCC has several subtypes that differ in their origin, molecular characteristics, and genetic makeup. Among them, clear cell RCC (ccRCC) and papillary RCC (pRCC) are two common subtypes, accounting for approximately 80% and 10–15% of RCC cases, respectively. The two subtypes differ in their appearance, with ccRCC typically showing clear-looking cancer cells and pRCC forming finger-like structures called papillae. However, molecular markers that can reliably help assess prognosis in these subtypes remain limited.
Now, by analyzing publicly available cancer databases, researchers at Tokyo University of Science (TUS), Japan, and Nippon Medical School, Japan, have found that high expression of a gene called CTD nuclear envelope phosphatase 1 (CTDNEP1) is associated with poorer survival outcomes in patients with ccRCC.
The study was led by Professor Tadayoshi Hayata at TUS and conducted by first author Ms. Mayuka Nii, a Ph.D. candidate at TUS, together with Mr. Kazutaka Ota, who was a third-year medical student at Nippon Medical School at the time of the study. Mr. Ota participated through Nippon Medical School's "Project Semester III" research placement course, which provides students with hands-on research experience under faculty supervision. This cross-institutional collaboration was a key aspect of the study. The findings of the research will be published in Volume 46, Issue 10 of the journal Anticancer Research on October 1, 2026.
"RCC is not a single disease, and we wanted to know whether a molecule we had studied in another cancer would behave the same way here. Our findings suggest that CTDNEP1 may serve as a candidate prognostic biomarker in RCC. Further experimental studies are required to clarify whether CTDNEP1 directly contributes to RCC progression," says Prof. Hayata.
CTDNEP1 encodes a phosphatase involved in intracellular signaling and lipid metabolism. Previous studies have suggested that abnormalities in CTDNEP1 may be associated with medulloblastoma, a malignant brain tumor in children. The present research group had also reported that low CTDNEP1 expression was associated with poor prognosis in pancreatic ductal adenocarcinoma. The findings reported here in ccRCC point in the opposite direction, indicating that the clinical meaning of CTDNEP1 expression depends on the cancer type. However, its biological function and clinical significance in many cancers remain unclear.
In this study, the researchers found that CTDNEP1 expression was higher in tumor tissue than in normal tissue across several cancer types, including RCC. This finding led the researchers to examine CTDNEP1 expression in 512 patients with ccRCC and 283 with pRCC using data from the TCGA Pan-Cancer Atlas. They divided patients into groups based on CTDNEP1 expression levels and compared survival outcomes while accounting for age, sex, and pathological stage.
Their results showed that patients with ccRCC who had higher levels of CTDNEP1 had significantly poorer survival outcomes, with the association particularly pronounced in Stage III disease. In the overall ccRCC cohort, the hazard ratio for overall survival in the high-expression group was 2.16 compared with the low-expression group. In Stage III ccRCC, high CTDNEP1 expression was significantly associated with poorer overall survival, disease-specific survival, and progression-free interval. However, no significant association was observed for disease-free interval. In contrast, the association between CTDNEP1 expression and prognosis was limited and inconsistent in patients with pRCC. No consistent association was observed for overall survival, disease-specific survival, or progression-free interval. The findings for disease-free interval varied depending on the statistical model used.
The researchers suggest that differences in the genetic and biological characteristics of ccRCC and pRCC may help explain these findings. The two subtypes have different genetic backgrounds and may arise from different types of kidney cells, while also developing within different tumor environments. These differences could influence the biological processes linked to CTDNEP1 expression.
The researchers identified different biological pathways linked to CTDNEP1 expression in the two RCC subtypes. In ccRCC, they observed an association between higher CTDNEP1 expression and immune- and inflammation-related pathways. In pRCC, they observed associations between CTDNEP1 expression and immune responses and metabolic processes, including pathways involved in energy production.
The study suggests that CTDNEP1 could be a candidate prognostic biomarker, particularly in ccRCC, although further experimental and clinical validation is needed. "In our earlier work on pancreatic cancer, low CTDNEP1 expression was associated with poor prognosis. Here we observed the opposite direction in ccRCC. The same molecule can carry a different clinical meaning depending on the cancer type and subtype," says Prof. Hayata.
However, the researchers note that their findings show an association rather than a direct cause-and-effect relationship and emphasize the need for further experiments to determine whether CTDNEP1 directly contributes to RCC progression. They also note that the stage-specific analyses were exploratory and based on limited patient numbers, and that the threshold used to separate high- and low-expression groups was derived from the same cohort, so validation in independent patient cohorts is required.
Reference
Title of original paper: CTDNEP1 Expression Is Associated With Subtype-dependent Prognostic Patterns in Renal Cell Carcinoma
Journal: Anticancer Research
DOI: https://doi.org/10.21873/anticanres.18397
About The Tokyo University of Science
Tokyo University of Science (TUS) is a well-known and respected university, and the largest science-specialized private research university in Japan, with four campuses in central Tokyo and its suburbs and in Hokkaido. Established in 1881, the university has continually contributed to Japan's development in science through inculcating the love for science in researchers, technicians, and educators.
With a mission of "Creating science and technology for the harmonious development of nature, human beings, and society," TUS has undertaken a wide range of research from basic to applied science. TUS has embraced a multidisciplinary approach to research and undertaken intensive study in some of today's most vital fields. TUS is a meritocracy where the best in science is recognized and nurtured. It is the only private university in Japan that has produced a Nobel Prize winner and the only private university in Asia to produce Nobel Prize winners within the natural sciences field.
Website: https://www.tus.ac.jp/en/mediarelations/
About Professor Tadayoshi Hayata from Tokyo University of Science
Dr. Tadayoshi Hayata is a Professor at the Department of Molecular Pharmacology, Faculty of Pharmaceutical Science at the Tokyo University of Science. His laboratory focuses on bone metabolism, cellular differentiation, molecular pharmacology, and similar fields to understand the nature of bone and joint diseases and find therapeutic targets. Prof. Hayata is affiliated with several Japanese Societies and the American Society for Bone and Mineral Research. He has published over 90 original articles and given over 70 presentations at academic conferences. In addition, his research on osteoporosis has made it to Japanese newspapers several times.
Funding information
Not available
