ArticleHepatology communications2025
Single-cell analyses unravel ecosystem dynamics and intercellular crosstalk during gallbladder cancer malignant transformation.
Article in Hepatology communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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2 citing papers in PubMed.
- Article
- Machine learning-driven classification and prognostic prediction of kidney renal clear cell carcinoma using APOBEC family expression signatures.Scientific reports · 2025Article
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8 authors.
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Abstract
backgroundGallbladder cancer (GBC) is a rare but aggressive malignancy, often detected late due to early asymptomatic stages. Understanding cellular and molecular changes from normal tissue to high-grade intraepithelial neoplasia (HGIN) and invasive GBC is vital for identifying early biomarkers and therapeutic targets.
methodsWe performed single-cell RNA sequencing on 98,113 cells derived from 2 normal adjacent tissues (NAT), 2 HGIN, and 6 GBC samples. The cellular diversity and heterogeneity, particularly within epithelial and immune cell populations in NAT-HGIN-GBC, were investigated utilizing single-cell RNA sequencing, bulk RNA sequencing (bulk RNA-seq), and 10 machine learning methodologies. Furthermore, the intercellular crosstalk between epithelial cells and tumor immune microenvironment cells was examined and validated through multiplex immunofluorescence staining.
resultsThe constructed cell atlas elucidated alterations in the immune landscape across various states of NAT-HGIN-GBC, highlighting a more pronounced inhibitory immune microenvironment in GBC. The epithelial subtype TOP2A+ Epi is markedly elevated in GBC and is correlated with a poor prognosis. Key genes associated with this subtype may include GMNN, CYTOR, KLK6, and BIRC5. Similarly, immunosuppressive macrophages, identified as TOP2A+ Macro, also increase along the NAT-HGIN-GBC sequence and are linked to reduced patient survival. Furthermore, TOP2A+ Macro and CD8+ exhausted T cells (CD8+ Tex) engage in intercellular communication with epithelial TOP2A+Epi cells via the TWEAK/FN14 signaling pathway, thereby promoting tumor progression and immune evasion in GBC. The findings were further corroborated through multiplex immunofluorescence staining conducted on specimens from patients.
conclusionsThis study elucidates significant alteration in the cellular ecosystems and intercellular signaling within the tumor immune microenvironment across the NAT-HGIN-GBC sequence. It identifies TOP2A, TWEAK, and FN14 as potential biomarkers and therapeutic targets for GBC.
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