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<p>Hepatocellular carcinoma (HCC) is a highly aggressive disease with a dismal prognosis. The recently described role of RNA pseudouridine modification in regulating anti-tumor immunity has attracted interest, but the understanding of its impact on hepatocellular carcinoma progression and immune evasion is limited. Here, we reveal that HCC could be categorized into pseudouridine-low, and -high subtypes with distinct clinicopathologic features, prognostic and tumor microenvironment. In general, the pseudouridine-high subtype presents a dismal prognosis with the immunosuppressive microenvironment. Inversely, the pseudouridine-low subtype was associated with favorable clinical outcomes with the immunoreactive microenvironment. Moreover, we develop and validate a pseudouridine-related prognostic model, which shows strong power for prognosis assessment. More&#xa0;importantly, we identified RPUSD3 as a critical pseudouridine modification gene. RPUSD3 knockdown inhibits hepatocellular carcinoma growth in vivo, increasing CD8 T cell infiltration. In conclusion, we established a novel HCC classification based on the RNA pseudouridine modification subtype. This classification had significant outcomes for estimating the prognosis, as well as the tumor microenvironment.</p>

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Identification of molecular subtypes based on pseudouridine modification in hepatocellular carcinoma

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年7月2日

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  • Weifeng Xu,
  • Caiyun Nie,
  • Zhen Liu,
  • Yingjun Liu,
  • Penghui Yu,
  • Huifang Lv,
  • Beibei Chen,
  • Jianzheng Wang,
  • Saiqi Wang,
  • Jing Zhao,
  • Yunduan He,
  • Shegan Gao,
  • Xiaobing Chen

摘要

Hepatocellular carcinoma (HCC) is a highly aggressive disease with a dismal prognosis. The recently described role of RNA pseudouridine modification in regulating anti-tumor immunity has attracted interest, but the understanding of its impact on hepatocellular carcinoma progression and immune evasion is limited. Here, we reveal that HCC could be categorized into pseudouridine-low, and -high subtypes with distinct clinicopathologic features, prognostic and tumor microenvironment. In general, the pseudouridine-high subtype presents a dismal prognosis with the immunosuppressive microenvironment. Inversely, the pseudouridine-low subtype was associated with favorable clinical outcomes with the immunoreactive microenvironment. Moreover, we develop and validate a pseudouridine-related prognostic model, which shows strong power for prognosis assessment. More importantly, we identified RPUSD3 as a critical pseudouridine modification gene. RPUSD3 knockdown inhibits hepatocellular carcinoma growth in vivo, increasing CD8 T cell infiltration. In conclusion, we established a novel HCC classification based on the RNA pseudouridine modification subtype. This classification had significant outcomes for estimating the prognosis, as well as the tumor microenvironment.