Spatial transcriptomics reveals the heterogeneity and FGG+CRP+ inflammatory cancer-associated fibroblasts replace islets in pancreatic ductal adenocarcinoma

Zhangyong Ren; Bing Pan; Fangfei Wang; Shaocheng Lyu; Jialei Zhai; Xiumei Hu; Zhe Liu; Lixin Li; Ren Lang; Qiang He; Xin Zhao

doi:10.3389/fonc.2023.1112576

Spatial transcriptomics reveals the heterogeneity and FGG+CRP+ inflammatory cancer-associated fibroblasts replace islets in pancreatic ductal adenocarcinoma

Front Oncol. 2023 Apr 14:13:1112576. doi: 10.3389/fonc.2023.1112576. eCollection 2023.

Authors

Zhangyong Ren¹, Bing Pan¹, Fangfei Wang¹, Shaocheng Lyu¹, Jialei Zhai², Xiumei Hu², Zhe Liu¹, Lixin Li¹, Ren Lang¹, Qiang He¹, Xin Zhao¹

Affiliations

¹ Department of Hepatobiliary Surgery, Beijing Chaoyang Hospital affiliated to Capital Medical University, Beijing, China.
² Department of Pathology, Beijing Chaoyang Hospital affiliated to Capital Medical University, Beijing, China.

Abstract

Background: Understanding the spatial heterogeneity of the tumor microenvironment (TME) in pancreatic cancer (PC) remains challenging.

Methods: In this study, we performed spatial transcriptomics (ST) to investigate the gene expression features across one normal pancreatic tissue, PC tissue, adjacent tumor tissue, and tumor stroma. We divided 18,075 spatial spots into 22 clusters with t-distributed stochastic neighbor embedding based on gene expression profiles. The biological functions and signaling pathways involved in each cluster were analyzed with gene set enrichment analysis.

Results: The results revealed that KRT13+FABP5+ malignant cell subpopulation had keratinization characteristics in the tumor tissue. Fibroblasts from adjacent tumor tissue exhibited a tumor-inhibiting role such as "B-cell activation" and "positive regulation of leukocyte activation." The FGG+CRP+ inflammatory cancer-associated fibroblasts replaced the islets in tumor stroma. During PC progression, the damage to pancreatic structure and function was heavier in the pancreatic exocrine (AMYA2+PRSS1+) than in the endocrine (INS+GCG+).

Conclusion: Our results revealed the spatial heterogeneity of dynamic changes and highlighted the significance of impaired exocrine function in PC.

Keywords: cancer-associated fibroblasts; heterogeneity; pancreatic ductal adenocarcinoma; spatial transcriptomics; tumor microenvironment.