Dendritic Cell-Related Gene Signature Identifies Pancreatic Cancer Subtypes and KCTD14-TNF Signaling Axis

Pancreatic cancer, characterized by a profoundly immunosuppressive tumor microenvironment, has a poor prognosis. Researchers at the Sichuan Cancer Hospital studied the role of dendritic cells (DCs) in pancreatic cancer and identified a novel DC-related gene signature that stratifies patient subtypes and implicates a KCTD14-TNF signaling axis. This study provides a foundation for integrating the dendritic cell-related risk score (DCRS) into clinical risk assessment and for pursuing KCTD14/TNFR1-targeted therapies to overcome DC-mediated immune suppression in pancreatic cancer.

Key Takeaways:

• A dendritic cell-related gene signature was identified in pancreatic cancer patients, which stratifies them into two immune phenotypes with distinct overall survival.
• The signature includes 130 overlapping DC-related genes enriched in immune pathways, indicating a crucial role of DCs in pancreatic cancer.
• The study highlights KCTD14 as a novel immunomodulatory oncogene acting through the TNF-TNFR1 axis, which may be targeted in therapies to overcome DC-mediated immune suppression.
• The dendritic cell-related risk score (DCRS) was constructed using LASSO-Cox regression and validated in independent cohorts.
• Single-cell RNA sequencing data from 25 PC samples were analyzed to identify cell-cell communication and pathway-specific analysis.
• Functional assays using KCTD14 knockdown in CAPAN-1 and PANC-1 cell lines demonstrated its impact on proliferation, migration, invasion, and TNF signaling.

Statistics:

• 130 overlapping DC-related genes were identified in the study.
• The dendritic cell-related gene signature stratified patients into two immune phenotypes with distinct overall survival (OS).
• The KCTD14-TNF signaling axis was implicated in the study.
• The dendritic cell-related risk score (DCRS) was validated in independent cohorts.
• 25 PC samples were analyzed using single-cell RNA sequencing data.

Sources:

• Dendritic cell-related gene signature in pancreatic cancer stratifies patient subtypes and implicates a KCTD14-TNF signaling axis, Frontiers in Immunology, 2025, 16.
• Yuxin Liang, Yuheng Gu, Zilong Zhang, Deyuan Zhong, Hongtao Yan, Yuhao Su, Yahui Chen, Fei Wang, Zhengwei Leng, Xiaolun Huang, Sichuan Cancer Hospital Researchers Provide New Insights into Pancreatic Cancer (Dendritic cell-related gene signature in pancreatic cancer stratifies patient subtypes and implicates a KCTD14-TNF signaling axis), Cancer Weekly, October 14, 2025, p 2199.