根据和二硫化物相关的糖酵解基因来构建一个预测肝细胞癌预后和免疫浸润分析的标志。
Based on disulfidptosis-related glycolytic genes to construct a signature for predicting prognosis and immune infiltration analysis of hepatocellular carcinoma.
发表日期:2023
作者:
Zhijian Wang, Xuenuo Chen, Jia Zhang, Xuanxin Chen, Jiayi Peng, Wenxiang Huang
来源:
Frontiers in Immunology
摘要:
肝细胞癌(HCC)包括几种不同的分子亚型,其预后意义不同。然而,至今尚未对基于与硫键脱氧和糖酵解相关的分子亚型及其相关代谢组学和免疫微环境的HCC预后标志进行全面分析。基于硫源相关的糖酵解基因(DRGGs)表达差异,将HCC患者分为不同亚型。建立并验证危险预后标记。最后,使用免疫组织化学(IHC)和定量实时聚合酶链反应(qRT-PCR)评估标记中关键基因SLCO1B1的表达水平。使用多重免疫荧光法探索该基因与免疫细胞的关联。通过细胞计数试剂盒-8,创口愈合和集落形成实验研究细胞的生物学功能。不同亚型的患者具有特定的临床病理特征,预后和免疫微环境。我们确定了七个有价值的基因,并构建了一个危险预后标记。风险评分分析显示,与高风险组相比,低风险组具有更好的预后,更高的免疫评分和更丰富的免疫相关通路,与肿瘤亚型一致。此外,IHC和qRT-PCR分析显示HCC组织中SLCO1B1的表达下降。功能实验显示,SLCO1B1的过表达抑制了HCC细胞的增殖,迁移和侵袭能力。我们开发了一个预后标记,可以帮助临床医生预测HCC患者的总生存期,并为靶向治疗提供参考价值。版权所有©2023 Wang, Chen, Zhang, Chen, Peng和Huang.
Hepatocellular carcinoma (HCC) comprises several distinct molecular subtypes with varying prognostic implications. However, a comprehensive analysis of a prognostic signature for HCC based on molecular subtypes related to disulfidptosis and glycolysis, as well as associated metabolomics and the immune microenvironment, is yet to be fully explored.Based on the differences in the expression of disulfide-related glycolytic genes (DRGGs), patients with HCC were divided into different subtypes by consensus clustering. Establish and verify a risk prognosis signature. Finally, the expression level of the key gene SLCO1B1 in the signature was evaluated using immunohistochemistry (IHC) and quantitative real-time PCR (qRT-PCR) in HCC. The association between this gene and immune cells was explored using multiplex immunofluorescence. The biological functions of the cell counting kit-8, wound healing, and colony formation assays were studied.Different subtypes of patients have specific clinicopathological features, prognosis and immune microenvironment. We identified seven valuable genes and constructed a risk-prognosis signature. Analysis of the risk score revealed that compared to the high-risk group, the low-risk group had a better prognosis, higher immune scores, and more abundant immune-related pathways, consistent with the tumor subtypes. Furthermore, IHC and qRT-PCR analyses showed decreased expression of SLCO1B1 in HCC tissues. Functional experiments revealed that SLCO1B1 overexpression inhibited the proliferation, migration, and invasion of HCC cells.We developed a prognostic signature that can assist clinicians in predicting the overall survival of patients with HCC and provides a reference value for targeted therapy.Copyright © 2023 Wang, Chen, Zhang, Chen, Peng and Huang.