Matches in SemOpenAlex for { <https://semopenalex.org/work/W4379984450> ?p ?o ?g. }
Showing items 1 to 58 of
58
with 100 items per page.
- W4379984450 abstract "<h3>Background</h3> Scirrhous hepatocellular carcinoma (SHCC) is one of the unique subtypes of hepatocellular carcinoma (HCC), characterized by abundant fibrous stroma in the tumor microenvironment. However, it remains unclear about the molecular traits of SHCC, which is essential to develop specialized therapeutic approaches for SHCC. <h3>Methods</h3> We presented an integrative analysis containing single-cell RNA-sequencing, whole-exome sequencing, and bulk RNA-sequencing in SHCC and usual HCC samples from 134 patients, to delineate genomic features, transcriptomic profiles, and stromal immune microenvironment of SHCC. Multiplexed immunofluorescence staining, flow cytometry and functional in-vitro experiments were performed for validation. <h3>Results</h3> SHCC presented with less genomic heterogeneity compared with usual HCC and mutations on druggable genes in SHCC mainly concentrated on main clones rather than subclones. Bulk transcriptomic subtyping demonstrated a higher prevalence of Boyault G1/G2 subtype, Hoshida S1/S2 subtype, Montiron inflamed subtype, and a conspicuous exclusion of CTNNB1 subtype in SHCC tumors in comparison with usual HCC tumors, indicating that SHCC represented a unique transcriptome profile distinct from usual HCC. Single-cell RNA-sequencing analysis revealed that insulin-like growth factor 2 (IGF2) was significantly upregulated in SHCC tumor cells compared to usual HCC, and could serve as a potential diagnostic biomarker for SHCC. Significant tumor stromal remodeling and hypoxia were observed in SHCC with the enrichment of matrix cancer-associated fibroblasts and upregulation of hypoxic pathways. Through single-cell trajectory and co-expression analysis, IGF2 was identified as a key mediator in shaping the hypoxic stromal microenvironment of SHCC. Under this microenvironment, SHCC exhibited an immunosuppressive niche correlated to enhanced vascular endothelial growth factor-A signaling activity, where CD4+T cells and CD8+T cells were dysfunctional. Furthermore, cell-cell interaction analysis and functional experiments showed that another hypoxic-related molecule secreted phosphoprotein 1 (SPP1) from SHCC tumor cells suppressed the function of dendritic cells via SPP1-CD44 axis, which also probably hindered the activation of T cells. <h3>Conclusions</h3> We uncovered the genomic characteristics of SHCC, and revealed a hypoxia-driven tumor stroma remodeling and immunosuppressive microenvironment in SHCC." @default.
- W4379984450 created "2023-06-10" @default.
- W4379984450 creator A5017584327 @default.
- W4379984450 creator A5031709547 @default.
- W4379984450 creator A5031906566 @default.
- W4379984450 creator A5032071728 @default.
- W4379984450 creator A5035163484 @default.
- W4379984450 creator A5089172668 @default.
- W4379984450 date "2023-06-01" @default.
- W4379984450 modified "2023-09-23" @default.
- W4379984450 title "IDDF2023-ABS-0068 Hypoxia-driven tumor stromal remodeling and immunosuppressive microenvironment in scirrhous hepatocellular carcinoma" @default.
- W4379984450 doi "https://doi.org/10.1136/gutjnl-2023-iddf.18" @default.
- W4379984450 hasPublicationYear "2023" @default.
- W4379984450 type Work @default.
- W4379984450 citedByCount "0" @default.
- W4379984450 crossrefType "proceedings-article" @default.
- W4379984450 hasAuthorship W4379984450A5017584327 @default.
- W4379984450 hasAuthorship W4379984450A5031709547 @default.
- W4379984450 hasAuthorship W4379984450A5031906566 @default.
- W4379984450 hasAuthorship W4379984450A5032071728 @default.
- W4379984450 hasAuthorship W4379984450A5035163484 @default.
- W4379984450 hasAuthorship W4379984450A5089172668 @default.
- W4379984450 hasConcept C104317684 @default.
- W4379984450 hasConcept C150194340 @default.
- W4379984450 hasConcept C162317418 @default.
- W4379984450 hasConcept C16930146 @default.
- W4379984450 hasConcept C2776107976 @default.
- W4379984450 hasConcept C2778019345 @default.
- W4379984450 hasConcept C3020616263 @default.
- W4379984450 hasConcept C502942594 @default.
- W4379984450 hasConcept C54355233 @default.
- W4379984450 hasConcept C86803240 @default.
- W4379984450 hasConceptScore W4379984450C104317684 @default.
- W4379984450 hasConceptScore W4379984450C150194340 @default.
- W4379984450 hasConceptScore W4379984450C162317418 @default.
- W4379984450 hasConceptScore W4379984450C16930146 @default.
- W4379984450 hasConceptScore W4379984450C2776107976 @default.
- W4379984450 hasConceptScore W4379984450C2778019345 @default.
- W4379984450 hasConceptScore W4379984450C3020616263 @default.
- W4379984450 hasConceptScore W4379984450C502942594 @default.
- W4379984450 hasConceptScore W4379984450C54355233 @default.
- W4379984450 hasConceptScore W4379984450C86803240 @default.
- W4379984450 hasLocation W43799844501 @default.
- W4379984450 hasOpenAccess W4379984450 @default.
- W4379984450 hasPrimaryLocation W43799844501 @default.
- W4379984450 hasRelatedWork W1963966397 @default.
- W4379984450 hasRelatedWork W2191316874 @default.
- W4379984450 hasRelatedWork W2551414968 @default.
- W4379984450 hasRelatedWork W2925764871 @default.
- W4379984450 hasRelatedWork W4284965464 @default.
- W4379984450 hasRelatedWork W4285807049 @default.
- W4379984450 hasRelatedWork W4312067415 @default.
- W4379984450 hasRelatedWork W4361823855 @default.
- W4379984450 hasRelatedWork W4361825591 @default.
- W4379984450 hasRelatedWork W4361826537 @default.
- W4379984450 isParatext "false" @default.
- W4379984450 isRetracted "false" @default.
- W4379984450 workType "article" @default.