A New Cuproptosis-Related lncRNAs Model for Predicting the Prognosis of Hepatitis B Virus-Associated Hepatocellular Carcinoma and Experimental Validation of LINC01269.

IF 2.1 4区 医学 Q2 MEDICINE, GENERAL & INTERNAL International Journal of General Medicine Pub Date : 2024-12-10 eCollection Date: 2024-01-01 DOI:10.2147/IJGM.S489059
Chuanbing Shi, Yintao Sun, Ling Sha, Xuefeng Gu
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Abstract

Background: Hepatocellular carcinoma (HCC) triggered by Hepatitis B virus (HBV) remains a significant clinical challenge, necessitating novel therapeutic interventions. Copper ionophores, recognized for introducing an innovative type of programmed cell death termed cuproptosis, present promising potentials for cancer therapy. Nevertheless, The role of cuproptosis-related lncRNAs (CRLRs) in HBV-HCC has not been clearly elucidated.

Methods: This study utilised univariate Cox, least absolute shrinkage and selection operator (LASSO), and multivariable Cox regression analyses to establish a signature for CRLRs in HBV-HCC. This prognostic model was validated with an independent internal validation cohort, combined with clinical parameters, and used to construct a nomogram for patient survival predictions. Gene Ontology (GO) and Gene Set Enrichment Analysis (GSEA) were employed to explore associated biological pathways. Additionally, a protein-protein interaction (PPI) network was developed, and implications for tumour mutational burden (TMB) and drug response were examined. A comprehensive bioinformatics analysis of these hub CRLRs was performed, followed by experimental validation through quantitative real-time PCR (qRT-PCR) and functional cellular assays.

Results: The nomogram showed high predictive accuracy for HBV-HCC patient survival. GO and GSEA analyses indicated that these lncRNAs are involved in pathways related to cancer and oestrogen metabolism. A PPI network consisting of 201 nodes and 568 edges was developed, and the TMB and drug response differed significantly between high- and low-risk groups. Analyses identified three hub CRLRs, SOS1-IT1, AC104695.3, and LINC01269, which were significantly differentially expressed in HCC tissues. In vitro, LINC01269 was found to enhance HCC cell proliferation, invasion, and migration.

Conclusion: The first systematic exploration of the roles of CRLRs in HBV-HCC demonstrates their critical involvement in the disease's pathogenesis and possible therapeutic implication. The distinct expression patterns and significant biological pathways suggest that these lncRNAs may facilitate novel therapeutic targets.

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预测乙型肝炎病毒相关肝细胞癌预后的新型杯突相关lncRNAs模型及LINC01269的实验验证
背景:由乙型肝炎病毒(HBV)引发的肝细胞癌(HCC)仍是一项重大的临床挑战,需要采取新的治疗干预措施。铜离子体被认为引入了一种创新的细胞程序性死亡,即杯突症,为癌症治疗带来了巨大的潜力。然而,杯突相关 lncRNAs(CRLRs)在 HBV-HCC 中的作用尚未明确阐明:本研究利用单变量 Cox、最小绝对收缩和选择算子(LASSO)以及多变量 Cox 回归分析建立了 CRLRs 在 HBV-HCC 中的特征。该预后模型通过独立的内部验证队列进行了验证,并与临床参数相结合,用于构建患者生存预测的提名图。基因本体(GO)和基因组富集分析(GSEA)被用来探索相关的生物通路。此外,还开发了蛋白质-蛋白质相互作用(PPI)网络,并研究了其对肿瘤突变负荷(TMB)和药物反应的影响。对这些中枢CRLRs进行了全面的生物信息学分析,然后通过定量实时PCR(qRT-PCR)和细胞功能测试进行了实验验证:结果:提名图显示了对 HBV-HCC 患者生存的高度预测准确性。GO和GSEA分析表明,这些lncRNA参与了与癌症和雌激素代谢相关的通路。建立了一个由201个节点和568条边组成的PPI网络,高危组和低危组的TMB和药物反应存在显著差异。分析发现,SOS1-IT1、AC104695.3 和 LINC01269 这三个中枢 CRLRs 在 HCC 组织中的表达存在显著差异。体外实验发现,LINC01269 能增强 HCC 细胞的增殖、侵袭和迁移:这是对 CRLRs 在 HBV-HCC 中作用的首次系统性探索,表明它们在该疾病的发病机制中起着关键作用,并可能具有治疗意义。不同的表达模式和重要的生物学途径表明,这些lncRNAs可能有助于找到新的治疗靶点。
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来源期刊
International Journal of General Medicine
International Journal of General Medicine Medicine-General Medicine
自引率
0.00%
发文量
1113
审稿时长
16 weeks
期刊介绍: The International Journal of General Medicine is an international, peer-reviewed, open access journal that focuses on general and internal medicine, pathogenesis, epidemiology, diagnosis, monitoring and treatment protocols. The journal is characterized by the rapid reporting of reviews, original research and clinical studies across all disease areas. A key focus of the journal is the elucidation of disease processes and management protocols resulting in improved outcomes for the patient. Patient perspectives such as satisfaction, quality of life, health literacy and communication and their role in developing new healthcare programs and optimizing clinical outcomes are major areas of interest for the journal. As of 1st April 2019, the International Journal of General Medicine will no longer consider meta-analyses for publication.
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