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Background <p>Hepatocellular carcinoma (HCC) is a prevalent type of malignant tumor known for its aggressive proliferation and invasive behavior. The exact molecular mechanisms underlying HCC development and progression remain unclear. Nevertheless, cuproptosis has been linked to a range of diseases, including cancers, resulting from imbalances in copper homeostasis. Here, a unique signature of long non-coding RNAs (lncRNAs) was developed, known as cuproptosis-related lncRNA (CRlncRNA). This signature has significant value in clinical practice for predicting prognosis and drug sensitivity in individuals with HCC.</p> Methods <p>The transcriptome data and clinical information were retrieved from the Cancer Genome Atlas (TCGA) database. The independent prognostic signature of five CRlncRNAs was constructed by co-expression analysis, Lasso Cox regression analysis, and univariate and multivariate Cox regression analysis. K-M analysis and ROC curve were used to evaluate the effectiveness of the signature in predicting prognosis and IC50 was used to predict the sensitivity of drugs. Furthermore, the differential expression of five CRlncRNAs was validated in clinical HCC samples, and functional in vitro experiments were performed to investigate the biological role of LINC02505, which is one of the five CRlncRNAs.</p> Results <p>Based on 374 HCC samples, a prognostic risk signature of five lncRNAs was constructed. High-risk patients showed significantly decreased survival periods, indicating that the CRlncRNA signature has predictive value in HCC. Combined with clinical and pathological information, the signature was shown to be an independent prognostic factor. Besides, the CRlncRNA signature was found to be closely associated with the efficacy of many commonly used chemotherapy drugs and targeted drugs for HCC patients. Additionally, further investigations showed that the mutation rate of HCC was related to the CRlncRNA signature, and gene enrichment analysis focused on immune-related pathways. Finally, among the CRlncRNA signature, LINC02505 was tested as a risk factor in vitro.</p> Conclusions <p>The CRlncRNA signature has significant clinical implications as it offers new biomarkers for evaluating HCC prognosis and guiding clinical medication.</p>

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Predicting prognosis and drug sensitivity in patients with hepatocellular carcinoma using an lncRNA signature associated with cuproptosis

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月4日

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  • Yan Li,
  • Shiyu Lv,
  • Yunqiu Wang

摘要

Background

Hepatocellular carcinoma (HCC) is a prevalent type of malignant tumor known for its aggressive proliferation and invasive behavior. The exact molecular mechanisms underlying HCC development and progression remain unclear. Nevertheless, cuproptosis has been linked to a range of diseases, including cancers, resulting from imbalances in copper homeostasis. Here, a unique signature of long non-coding RNAs (lncRNAs) was developed, known as cuproptosis-related lncRNA (CRlncRNA). This signature has significant value in clinical practice for predicting prognosis and drug sensitivity in individuals with HCC.

Methods

The transcriptome data and clinical information were retrieved from the Cancer Genome Atlas (TCGA) database. The independent prognostic signature of five CRlncRNAs was constructed by co-expression analysis, Lasso Cox regression analysis, and univariate and multivariate Cox regression analysis. K-M analysis and ROC curve were used to evaluate the effectiveness of the signature in predicting prognosis and IC50 was used to predict the sensitivity of drugs. Furthermore, the differential expression of five CRlncRNAs was validated in clinical HCC samples, and functional in vitro experiments were performed to investigate the biological role of LINC02505, which is one of the five CRlncRNAs.

Results

Based on 374 HCC samples, a prognostic risk signature of five lncRNAs was constructed. High-risk patients showed significantly decreased survival periods, indicating that the CRlncRNA signature has predictive value in HCC. Combined with clinical and pathological information, the signature was shown to be an independent prognostic factor. Besides, the CRlncRNA signature was found to be closely associated with the efficacy of many commonly used chemotherapy drugs and targeted drugs for HCC patients. Additionally, further investigations showed that the mutation rate of HCC was related to the CRlncRNA signature, and gene enrichment analysis focused on immune-related pathways. Finally, among the CRlncRNA signature, LINC02505 was tested as a risk factor in vitro.

Conclusions

The CRlncRNA signature has significant clinical implications as it offers new biomarkers for evaluating HCC prognosis and guiding clinical medication.