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: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
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| 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. |
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| ISSN: | 1475-2867 |