HCC spatial transcriptomic profiling reveals significant and potentially targetable cancer-endothelial interactions

Chenyue Lu, Amaya Pankaj, Michael Raabe, Cole Nawrocki, Ann Liu, Nova Xu, Bidish K. Patel, Matthew J. Emmett, Avril K. Coley, Cristina R. Ferrone, Vikram Deshpande, Irun Bhan, Yujin Hoshida, David T. Ting, Martin J. Aryee, Joseph W. Franses

Research output: Contribution to journalArticlepeer-review

Abstract

Background: HCC is a highly vascular tumor, and many effective drug regimens target the tumor blood vessels. Prior bulk HCC subtyping data used bulk transcriptomes, which contained a mixture of parenchymal and stromal contributions. Methods: We utilized computational deconvolution and cell-cell interaction analyses to cell type-specific (tumor-enriched and vessel-enriched) spatial transcriptomic data collected from 41 resected HCC tissue specimens. Results: We report that the prior Hoshida bulk transcriptional subtyping schema is driven largely by an endothelial fraction, show an alternative tumor-specific schema has potential prognostic value, and use spatially paired ligand-receptor analyses to identify known and novel (LGALS9 tumor-HAVCR2 vessel) signaling relationships that drive HCC biology in a subtype-specific and potentially targetable manner. Conclusions: Our study leverages spatial gene expression profiling technologies to dissect HCC heterogeneity and identify heterogeneous signaling relationships between cancer cells and their endothelial cells. Future validation and expansion of these findings may validate novel cancer-endothelial cell interactions and related drug targets.

Original languageEnglish
Article numbere0533
JournalHepatology Communications
Volume8
Issue number10
DOIs
StatePublished - Sep 2024
Externally publishedYes

Keywords

  • hcc
  • liver cancer
  • spatial profiling
  • tumor microenvironment

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