Intercellular Communication Between FAP+ Fibroblasts and SPP1+ Macrophages in Prostate Cancer via Multi-Omics

Tingting Wu^1*Xinyu Li²Fei Zheng³Hanchao Liu⁴Yang Yu^5*

• ¹Shenzhen Qianhai Taikang Hospital, Shenzhen, China
• ²Department of Urology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
• ³Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, China
• ⁴Department of Andrology and Urology, Sir Run Run Shaw Hospital, affiliated with the Zhejiang University School of Medicine, Hangzhou, China
• ⁵Department of General Surgery, Chifeng Hospital, Chifeng, Inner Mongolia, China

Prostate cancer (PCa) presents substantial heterogeneity and unpredictability in its progression.Despite therapeutic advancements, mortality from advanced PCa remains a significant challenge. Understanding the intercellular communication within the tumor microenvironment (TME) is critical for uncovering mechanisms driving tumorigenesis and identifying novel therapeutic targets.We employed an integrative approach combining bulk RNA sequencing, single-cell RNA sequencing (scRNA-seq), and spatial transcriptomics to investigate interactions between FAP+ fibroblasts and tumor-associated macrophages in PCa. Key findings were validated using immunohistochemical and immunofluorescence staining techniques.Analysis of 23,519 scRNA-seq data from 23 prostate samples revealed a pronounced accumulation of FAP+ fibroblasts in tumor tissues. Spatial transcriptomics and bulk RNA sequencing demonstrated strong associations between FAP+ fibroblasts and SPP1+ macrophages. Notably, tumor-specific intercellular signaling pathways, such as CSF1/CSF1R and CXCL/ACKR1, were identified, highlighting their potential role in fostering an immunosuppressive TME.Our findings unveil a distinct pattern of crosstalk between FAP+ fibroblasts and SPP1+ macrophages in PCa, shedding light on potential therapeutic targets for advanced PCa.