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<p>The significance of tertiary lymphoid structures (TLS) in hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) remains ambiguous. This study evaluates the prognostic impact of intra-tumoral TLS (iTLS) and peri-tumoral TLS (pTLS) and explores the interplay between TLS and cancer-associated fibroblasts (CAF) in patients undergoing curative hepatic resection. A retrospective analysis of 83 HCC patients with PVTT assessed the prognostic value of TLS. Transcriptomic data were mined to identify TLS- and CAF-related genes, and a seven-gene prognostic model was constructed using LASSO and Cox regression analyses. Immune microenvironment, mutation characteristics, and response to immunotherapy were analyzed between risk groups. iTLS + and high pTLS density were independently associated with improved overall survival (OS), but not recurrence-free survival (RFS) or early recurrence. A novel risk model comprising KLF2, HBEGF, KLRB1, PGF, JAM2, CHORDC1, and YTHDF2 stratified patients into high- and low-risk groups, with the high-risk group demonstrating poorer OS and diminished immunotherapy responsiveness. Low-risk patients exhibited higher immune infiltration (e.g., B cells, T cells) and stronger antitumor activity, whereas high-risk tumors showed active proliferation and immune evasion. iTLS and pTLS are independent predictors of favorable OS in HCC patients with PVTT. The TLS/CAF-based risk model offers robust prognostic utility and highlights distinct biological and immune features between patient subgroups. These findings provide a foundation for personalized prognostic assessment and therapeutic decision-making in advanced HCC.</p>

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Prognostic impact of tertiary lymphoid structures and cancer-associated fibroblasts in hepatocellular carcinoma with portal vein tumor thrombus

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月23日

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  • Lingbo Hu,
  • Cong Chen,
  • Yanhong Xiao,
  • Zhenghang Li,
  • Ning Jiang,
  • Chengyou Du,
  • Guirong Lv,
  • Jun Tang,
  • Bo Zeng

摘要

The significance of tertiary lymphoid structures (TLS) in hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) remains ambiguous. This study evaluates the prognostic impact of intra-tumoral TLS (iTLS) and peri-tumoral TLS (pTLS) and explores the interplay between TLS and cancer-associated fibroblasts (CAF) in patients undergoing curative hepatic resection. A retrospective analysis of 83 HCC patients with PVTT assessed the prognostic value of TLS. Transcriptomic data were mined to identify TLS- and CAF-related genes, and a seven-gene prognostic model was constructed using LASSO and Cox regression analyses. Immune microenvironment, mutation characteristics, and response to immunotherapy were analyzed between risk groups. iTLS + and high pTLS density were independently associated with improved overall survival (OS), but not recurrence-free survival (RFS) or early recurrence. A novel risk model comprising KLF2, HBEGF, KLRB1, PGF, JAM2, CHORDC1, and YTHDF2 stratified patients into high- and low-risk groups, with the high-risk group demonstrating poorer OS and diminished immunotherapy responsiveness. Low-risk patients exhibited higher immune infiltration (e.g., B cells, T cells) and stronger antitumor activity, whereas high-risk tumors showed active proliferation and immune evasion. iTLS and pTLS are independent predictors of favorable OS in HCC patients with PVTT. The TLS/CAF-based risk model offers robust prognostic utility and highlights distinct biological and immune features between patient subgroups. These findings provide a foundation for personalized prognostic assessment and therapeutic decision-making in advanced HCC.