ArticleHepatology communications2026
Construction of TLS-related gene signature for predicting prognosis and immunotherapy response in hepatocellular carcinoma.
Article in Hepatology communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Molecular biomarkers for diagnosis, prognosis, precision therapy, and immunotherapy in cholangiocarcinoma, cHCC-CCA, and HCC.Hepatology communications · 2026Review
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12 authors.
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Abstract
backgroundTertiary lymphoid structures (TLSs) are critical components of the tumor microenvironment in HCC. However, the role of TLS-related molecules in predicting HCC outcomes and guiding immunotherapy remains unexplored. This study aimed to develop TLS-related gene signature (TLSRS) to predict prognosis and immunotherapy response in patients with HCC.
methodsTLS-related genes (TLSRGs) were identified through differential gene expression analysis combined with weighted correlation network analysis. TLSRGs were selected to take the intersection and LASSO regression to construct a TLSRS. Following validation of the associations between clinical prognosis and TLS-related gene features, analyses were further expanded to GSEA, HCC molecular classes, tumor microenvironment characteristics, immune-related molecular features and immunotherapy responsiveness. TLSRS was further explored using single-cell, spatial transcriptomics, immunohistochemistry, and multiplex immunofluorescence to determine their relationship with TLS.
resultsTLSs are identified as a favorable prognostic factor in HCC. Three TLSRGs (ACKR1, CCR7, and IL7R), which were associated with both TLS presence and prognosis, were constructed with TLSRS. The TLSRS-high group, which was associated with inflammation-related HCC molecular subtypes, exhibited significantly improved clinical outcomes, along with enhanced immune cell infiltration, enriched immune response pathways, and a higher probability of response to immunotherapy. Results from single-cell, spatial transcriptomics, immunohistochemistry, and multiplex immunofluorescence revealed that ACKR1, CCR7, and IL7R shared similar expression patterns and spatial localization with TLS.
conclusionsThe TLSRS shows a correlation with both prognosis and immunotherapy response in patients with HCC, suggesting its potential value in advancing precision medicine for HCC.
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