Abstract 152P
Background
Microvascular invasion (MVI) represents a well-acknowledged aggressive pattern in intrahepatic cholangiocarcinoma (ICC), significantly influencing postoperative recurrence risk. However, its phenotypic characteristics and spatial organization have remained poorly understood.
Methods
To address these limitations, we conducted a comprehensive spatial analysis based on data from over 29,632 spots across six samples.
Results
Initially, we manually delineated MVI clusters using the cloupe software, revealing heightened proliferation and angiogenesis activities within MVI regions. Notably, we identified CXCL5 and SLC6A14 as potential biomarkers for MVI, which were also found to be highly expressed in tumor invasive areas. Furthermore, transcription factors SOX10, ZEB1, and SNAI2 exhibited enhanced expression in MVI, thereby promoting tumor proliferation, migration, and epithelial-mesenchymal transition. CXCL5 was validated as a serum marker to predict vascular invasion with an AUC of 0.92 and intrahepatic metastasis with an AUC of 0.96 in a substantial in-house cohort comprising 135 patients. High expression levels of CXCL5 and SLC6A14 were associated with poorer survival outcomes, with patients exhibiting high expression of both genes demonstrating the worst outcome. Importantly, our findings unveiled the ability of MVI and its progenitor cells to recruit immunosuppressive MRC1+ macrophages. Additionally, we observed elevated expression of numerous immune checkpoints, including HAVCR2 and TIGHT, in this microenvironment, indicating immune resistance. Moreover, we identified CXCL5-CXCR2 and LGALS9-HAVCR2 as the principal ligand-receptor pairs involved in cell-cell communication between MVI and MRC1+ macrophages.
Conclusions
In summary, our study elucidates the roles of CXCL5 and SLC6A14 as markers of MVI and provides valuable insights into the unique spatial structures of MVI that contribute to immune resistance.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.