综合分析确定长非编码RNARNASEH1-AS1作为潜在的预后生物标志物和肝细胞癌的瘤标
Jin Sun1,2,3, Yingnan Li3, Hongwei Tian1,2,3
1National and Local Joint Engineering Research Center of Biodiagnostics and Biotherapy, Xi'an Jiaotong University Xi'an, Shaanxi, China.
American journal of cancer research
|April 9, 2024
概括
长非编码RNARNASEH1-AS1在肝细胞癌 (HCC) 中被上调,与预后不佳和免疫细胞透率降低相关. 这种致癌性 lncRNA 显示出作为 HCC 的诊断和预后生物标志物的潜力.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 基因组学就是基因组学.
背景情况:
- 长非编码RNAs (lncRNAs) 越来越多地被认为是癌症进展中的角色.
- 在肝细胞癌 (HCC) 中RNASEH1-AS1的特定参与尚未完全阐明.
- 了解lncRNA表达模式对于识别新型癌症生物标志物和治疗点至关重要.
研究的目的:
- 研究RNASEH1-AS1在HCC中的表达和临床意义.
- 确定与RNASEH1-AS1共同表达的基因,并探索它们在HCC中的功能途径.
- 为HCC患者开发基于RNASEH1-AS1及其相关基因的预后模型.
主要方法:
- 对癌症基因组图谱 (TCGA) 数据的分析,以评估RNASEH1-AS1表达,与临床病理特征的相关性,预后和免疫细胞透.
- 生物信息分析包括相关性分析,基因本体学 (GO) 和KEGG通路丰富,以及蛋白质-蛋白质相互作用 (PPI) 网络构建,以确定共同表达的基因和枢纽基因.
- 单变Cox和最小绝对选择运算符 (LASSO) 回归用于风险模型构建,随后在HCC组织和细胞系中进行实验验证,包括敲击实验和机制研究.
主要成果:
- RNASEH1-AS1在HCC中显著上调,并与预后不佳,组织学等级较高和AFP水平升高有关,显示出良好的诊断和预后价值.
- RNASEH1-AS1的表达与关键免疫细胞的透相反相关,包括血类树突细胞 (pDC),B细胞和中性粒细胞.
- 基于四个枢纽基因 (EIF4A3,WDR12,DKC1,NAT10) 的风险模型显示出强大的预后预测潜力;实验验证证证了RNASEH1-AS1在HCC扩散,迁移和入侵中的致癌作用,DKC1调节其稳定性.
结论:
- 在HCC中,RNASEH1-AS1作为致癌性lncRNA的功能,促进瘤进展.
- 作为肝细胞癌的诊断和预后生物标志物,RNASEH1-AS1具有显著的潜力.
- 对RNASEH1-AS1及其监管网络的进一步研究可能为HCC提供新的治疗策略.
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