An integrative analysis revealing cuproptosis-related lncRNAs signature as a novel prognostic biomarker in hepatocellular carcinoma

Frontiers in Genetics

Genetics

Wenjie Huang¹  Bixiang Zhang¹  Xiaoyu Ji¹  Mengyu Sun¹  Meng Xie¹  Xiaoping Chen¹  Weibo Feng²  Jie Chen²  Xilang Chen²  Kaichun Wu²  Yongzhan Nie²  Daiming Fan²  Limin Xia³ 

[1] Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China;State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi, China;State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi, China;Hubei Key Laboratory of Hepato-Pancreato-Biliary Diseases, Department of Gastroenterology, Institute of Liver and Gastrointestinal Diseases, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China;

关键词: hepatocellular carcinoma;    cuproptosis;    lncRNAs;    prognostic signature;    immune infiltration;   

DOI  :  10.3389/fgene.2023.1056000

 received in 2022-09-28, accepted in 2023-01-27,  发布年份 2023

来源: Frontiers

【 摘 要 】

Background: Cuproptosis is a newly defined form of cell death, whether cuproptosis involved in hepatocellular carcinoma (HCC) remains elusive.Method: We obtained patients’ RNA expression data and follow-up information from University of California Santa Cruz (UCSC) and The Cancer Genome Atlas (TCGA). We analyzed the mRNA level of Cuproptosis-related genes (CRGs) and performed univariate Cox analysis. Liver hepatocellular carcinoma (LIHC) was chosen for further investigation. Real-Time quantitative PCR (RT-qPCR), Western blotting (WB), Immunohistochemical (IHC), and Transwell assays were used to determine expression patterns and functions of CRGs in LIHC. Next, we identified CRGs-related lncRNAs (CRLs) and differentially expressed CRLs between HCC and normal cases. Univariate Cox analysis, least absolute shrinkage selection operator (LASSO) analysis and Cox regression analysis were used to construct the prognostic model. Univariate and multivariate Cox analysis was used to assess whether the risk model can act as an independent risk factor of overall survival duration. Different risk groups performed immune correlation analysis, tumor mutation burden (TMB), and Gene Set Enrichment Analysis (GSEA) analysis were performed in different risk groups. Finally, we assessed the performance of the predictive model in drug sensitivity.Results: CRGs expression levels have significant differences between tumor and normal tissues. High expression of Dihydrolipoamide S-Acetyltransferase (DLAT) correlated to metastasis of HCC cells and indicated poor prognosis for HCC patients. Our prognostic model consisted of four cuproptosis-related lncRNA (AC011476.3, AC026412.3, NRAV, MKLN1-AS). The prognostic model performed well in predicting survival rates. The results from Cox regression analysis suggested that risk score can serve as an independent prognostic element for survival durations. Survival analysis revealed that low risk patients have extended survival periods compared with those with high risk. The results of the immune analysis indicated that risk score has a positive correlation with B cell and CD4+ T cell Th2, while has a negative relationship with endothelial cell and hematopoietic cells. Besides, immune checkpoint genes have higher expression folds in the high-risk set than in the low-risk set. The high-risk group had higher rates of genetic mutation than the low-risk set while having a shorter survival time. GSEA revealed the signaling pathways enriched in the high-risk group were mostly immune-related, while metabolic-related pathways were enriched in the low-risk group. Drugs sensitivity analysis indicated that our model has the ability to predict the efficacy of clinical treatment.Conclusion: The Cuproptosis-related lncRNAs prognostic formula is a novel predictor of HCC patients’ prognosis and drug sensitivity.

【 授权许可】

Unknown   
Copyright © 2023 Chen, Sun, Feng, Chen, Ji, Xie, Huang, Chen, Zhang, Nie, Fan, Wu and Xia.