articleCell DiscoveryJan 28, 2025GOLD OA

Stromal architecture and fibroblast subpopulations with opposing effects on outcomes in hepatocellular carcinoma

Fudan University · Zhongshan Hospital · +11 more institutions

PubMed
Indexed incrossrefdoajpubmed

Abstract

Dissecting the spatial heterogeneity of cancer-associated fibroblasts (CAFs) is vital for understanding tumor biology and therapeutic design. By combining pathological image analysis with spatial proteomics, we revealed two stromal archetypes in hepatocellular carcinoma (HCC) with different biological functions and extracellular matrix compositions. Using paired single-cell RNA and epigenomic sequencing with Stereo-seq, we revealed two fibroblast subsets CAF-FAP and CAF-C7, whose spatial enrichment strongly correlated with the two stromal archetypes and opposing patient prognosis. We discovered two functional units, one is the intratumor inflammatory hub featured by CAF-FAP plus CD8_PDCD1 proximity and the…

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