Identification of molecular subtypes based on pseudouridine modification in hepatocellular carcinoma

Abstract 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 immu...

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Main Authors: 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
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Cancer Cell International
Online Access:https://doi.org/10.1186/s12935-025-03844-5
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Summary:Abstract 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.
ISSN:1475-2867