Mapping cell type-resolved transcriptomic profiles to patient survival in pancreatic cancer

  • Cancer Cell. 2026 Jun 11:S1535-6108(26)00257-6. doi: 10.1016/j.ccell.2026.05.012.
Rong Tang  1 ,  Liquan Jin  2 ,  Chen Chen  3 ,  Yingna Liao  4 ,  Dingru Li  5 ,  Yangyi Li  6 ,  Yueyue Chen  7 ,  Yuan Liu  8 ,  Qiong Du  9 ,  Zeyin Rong  1 ,  Jiaoshun Chen  2 ,  Yubin Lei  10 ,  Zijian Wu  11 ,  Zhen Tan  12 ,  Yufeng Wang  1 ,  Haoyu Wang  13 ,  Jin Xu  1 ,  Wei Wang  14 ,  Si Shi  15 ,  Xianjun Yu  16
Affiliations
  • 1. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200030, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200030, China.
  • 2. Shanghai Pancreatic Cancer Institute, Shanghai 200032, China; Shanghai Key Laboratory of Precision Medicine for Pancreatic Cancer, Shanghai 200032, China.
  • 3. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200030, China.
  • 4. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200030, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
  • 5. Shanghai Pancreatic Cancer Institute, Shanghai 200032, China.
  • 6. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200030, China.
  • 7. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200030, China; Shanghai Key Laboratory of Precision Medicine for Pancreatic Cancer, Shanghai 200032, China.
  • 8. Department of Endoscopy, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
  • 9. Department of Pharmacy, Fudan University Shanghai Cancer Center, Shanghai 200032, China.
  • 10. Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, Zhejiang Province 310030, China.
  • 11. Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China.
  • 12. Department of Hepatobiliary Pancreatic Surgery, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China.
  • 13. Clinical Medical College of Dali University, Dali, Yunnan 671003, China.
  • 14. Shanghai Pancreatic Cancer Institute, Shanghai 200032, China; Pancreatic Cancer Institute, Fudan University, Shanghai 200032, China.
  • 15. Shanghai Pancreatic Cancer Institute, Shanghai 200032, China; Shanghai Key Laboratory of Precision Medicine for Pancreatic Cancer, Shanghai 200032, China. Electronic address: [email protected].
  • 16. Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200030, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200030, China. Electronic address: [email protected].
PMID: 42276047 DOI: 10.1016/j.ccell.2026.05.012
Abstract

Traditional bulk-level transcriptomic Sequencing cannot link cell type-specific gene expression to patient survival. In this study, we integrate single-nucleus RNA-seq and longitudinal data from 152 patients with pancreatic ductal adenocarcinoma (PDAC), profiling 1.2 million cells to construct a prognostic map connecting cell type-resolved gene expression with overall survival. Using a single-cell-resolved spatial transcriptomic platform, we further analyze 3.1 million cells and correlate their spatial distribution with therapeutic response. To empower the translational research community, we develop ctPANDA, an interactive platform offering cell-type-level prognostic insights. This atlas identifies PLOD2 as a promising target, with elevated expression predicting poorer outcomes across eight cell types. We have developed a proof-of-concept compound that can effectively degrade PLOD2 and inhibit PDAC progression in vivo. Collectively, this study advances the prognostic analysis from bulk-level to cell-type resolution, establishing a framework linking gene expression to clinical outcomes and providing actionable insights for target discovery and precision oncology.

Keywords
patient prognosis; precision treatment; single-nucleus transcriptome; translational medicine.
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