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Objective <p>Hepatocellular carcinoma (HCC) is a lethal malignancy with limited prognostic biomarkers. This study aimed to develop an RNA methylation-related long non-coding RNA (lncRNA) signature to predict survival and guide therapy in HCC.</p> Methods <p>Transcriptomic and clinical data from 374 HCC tissues (TCGA) were analyzed. RNA methylation-related lncRNAs were identified (Pearson correlation, |cor|&gt; 0.4, <i>p</i> &lt; 0.001). A prognostic signature was constructed using univariate Cox and LASSO regression. Patients were stratified into high-/low-risk groups, validated for survival, immune infiltration, and drug response.</p> Results <p>A robust three-lncRNA signature (SNHG30, AL049840.5, NRAV) was established. High-risk patients showed significantly worse overall survival (<i>p</i> &lt; 0.001) and progression-free survival (<i>p</i> &lt; 0.001) compared to low-risk patients. The risk score emerged as an independent prognostic factor (multivariate Cox, <i>p</i> &lt; 0.001) with strong predictive accuracy (1-/3-/5-year AUCs: 0.717/0.686/0.682). Functional analysis revealed distinct biological pathways between risk groups, with high-risk tumors associated with cell cycle dysregulation and immune suppression (higher TIDE scores), while low-risk tumors exhibited metabolic pathway activation. Drug sensitivity analysis suggested differential responses to chemotherapy and targeted therapies between risk groups.</p> Conclusion <p>Our study developed and validated a clinically applicable RNA methylation-related lncRNAs signature that effectively predicts HCC prognosis and therapeutic response. This signature provides valuable insights for risk stratification and may guide personalized treatment decisions in HCC management.</p>

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Establishment and validation of RNA methylation-related lncRNAs signature that predicts prognosis and potential targeted therapy in hepatocellular carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月16日

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  • Yunchuan Yang,
  • Xiang Ma,
  • Chi Zhou,
  • Zhongzheng Ma,
  • Junyi Huo,
  • Zhengxin Zhao,
  • Peiyuan Cui,
  • Lei Zhou

摘要

Objective

Hepatocellular carcinoma (HCC) is a lethal malignancy with limited prognostic biomarkers. This study aimed to develop an RNA methylation-related long non-coding RNA (lncRNA) signature to predict survival and guide therapy in HCC.

Methods

Transcriptomic and clinical data from 374 HCC tissues (TCGA) were analyzed. RNA methylation-related lncRNAs were identified (Pearson correlation, |cor|> 0.4, p < 0.001). A prognostic signature was constructed using univariate Cox and LASSO regression. Patients were stratified into high-/low-risk groups, validated for survival, immune infiltration, and drug response.

Results

A robust three-lncRNA signature (SNHG30, AL049840.5, NRAV) was established. High-risk patients showed significantly worse overall survival (p < 0.001) and progression-free survival (p < 0.001) compared to low-risk patients. The risk score emerged as an independent prognostic factor (multivariate Cox, p < 0.001) with strong predictive accuracy (1-/3-/5-year AUCs: 0.717/0.686/0.682). Functional analysis revealed distinct biological pathways between risk groups, with high-risk tumors associated with cell cycle dysregulation and immune suppression (higher TIDE scores), while low-risk tumors exhibited metabolic pathway activation. Drug sensitivity analysis suggested differential responses to chemotherapy and targeted therapies between risk groups.

Conclusion

Our study developed and validated a clinically applicable RNA methylation-related lncRNAs signature that effectively predicts HCC prognosis and therapeutic response. This signature provides valuable insights for risk stratification and may guide personalized treatment decisions in HCC management.