2. Academic Validation
  3. Single-cell transcriptome analysis identifies MIF as a novel tumor-associated neutrophil marker for pancreatic ductal adenocarcinoma

Single-cell transcriptome analysis identifies MIF as a novel tumor-associated neutrophil marker for pancreatic ductal adenocarcinoma

  • NPJ Precis Oncol. 2025 Aug 20;9(1):293. doi: 10.1038/s41698-025-01085-3.
Yan Zeng # 1,  Jiaping Yu # 1,  Yutong Chen # 1 2,  Juan Zhuang 1,  Xinyue Liang 1,  Yaning Li 1,  Shili Chen 3,  Wenzheng Pang 4,  Linjuan Zeng 5
Affiliations

Affiliations

  • 1 Department of Abdominal Oncology, the Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China.
  • 2 Department of Oncology, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian, China.
  • 3 Department of Abdominal Oncology, the Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China. chenshli7@mail.sysu.edu.cn.
  • 4 Department of Abdominal Oncology, the Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China. pwenzh@mail.sysu.edu.cn.
  • 5 Department of Abdominal Oncology, the Cancer Center of the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong, China. zenglinj@mail.sysu.edu.cn.
  • # Contributed equally.
PMID: 40835726 DOI: 10.1038/s41698-025-01085-3
Abstract

Pancreatic Cancer is a common cause of Cancer mortality, and pancreatic ductal adenocarcinoma (PDAC) is the most common subtype. Tumor-associated neutrophils (TANs) have been recognized as potential therapeutic targets. In this study, we utilized bulk and single-cell RNA Sequencing (scRNA‒seq) to identify seven distinct subtypes of neutrophils in PDAC. Oxidized low-density lipoprotein receptor 1 (OLR1)+ neutrophils and macrophage migration inhibitory factor (MIF)+ neutrophils were classified as TANs. The clinical relevance, dynamic transitional process, function, cell‒cell communication and transcription factor activity of neutrophil subclusters in PDAC were characterized. Furthermore, the novel MIF+ TANs were fully validated in PDAC tissues, an orthotopic pancreatic tumor model and a patient-derived xenograft (PDX) model. MIF+ TANs promote the proliferation and migration of PDAC cells through the activation of the ERK and Akt pathways and epithelial‒mesenchymal transition (EMT). This study provides insight into the potential of MIF+ TANs as therapeutic targets for PDAC patients.

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