解码基于ARF4和eif5b的肝细胞癌射频消融不充分后的预后特征和免疫景观:通过多组学和实验验证

IF 4.2 3区 医学 Q2 ONCOLOGY
Journal of Hepatocellular Carcinoma Pub Date : 2025-05-09 eCollection Date: 2025-01-01 DOI:10.2147/JHC.S517528
Yixin Zhang, Yongpan Lu, Sui Zheng, Wanrong Luo, Min Tan, Baoming Luo
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引用次数: 0

摘要

背景:射频消融(RFA)是非手术治疗肝细胞癌(HCC)的关键,但其术后复发风险高,超过传统手术。不充分的肿瘤消融可能引发免疫反应,促进肿瘤局部进展。因此,本研究旨在确定免疫生物标志物,以提高RFA患者的治疗精度和预后准确性。方法:本研究利用来自癌症基因组图谱(TCGA)、基因表达图谱(GEO)和国际癌症基因组联盟(ICGC)数据库的数据,研究影响射频消融(IRFA)患者预后的新型免疫生物标志物。随后,开发并验证了IRFA模型。然后,我们采用定量实时聚合酶链反应(qPCR)、Western blotting (WB)、免疫组织化学(IHC)和免疫荧光(IF)技术对人肝癌细胞系和IRFA动物模型进行验证,验证IRFA后adp -核糖基化因子4 (ARF4)和真核翻译起始因子5B (EIF5B)的表达及其与预后的相关性。此外,通过下调ARF4和EIF5B来评估细胞增殖、迁移、侵袭和上皮-间质转化(EMT)。最后,随后进行转录组测序以证实和扩展我们的发现。结果:ARF4和EIF5B被确定为影响IRFA患者预后的关键免疫靶点,构成了IRFA风险模型的基础。该模型中的高风险评分与多种癌症类型的预后较差和对免疫检查点抑制剂(ICIs)的反应性降低相关。实验验证证实了ARF4和EIF5B在IRFA结果中的保护作用,而敲低实验表明它们在IRFA模型中参与促进细胞增殖、迁移、侵袭和EMT,可能通过转录组测序显示的P53和转化生长因子β (TGF-β)信号通路激活等途径。结论:ARF4和EIF5B作为影响肝细胞癌RFA患者预后的生物标志物具有良好的潜力。这些发现表明它们可以作为缓解rfa后HCC复发的可行治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Decoding ARF4 and EIF5B-Based Prognostic Signatures and Immune Landscape Following Insufficient Radiofrequency Ablation in Hepatocellular Carcinoma: Through Multi-Omics and Experimental Validation.

Background: Radiofrequency ablation (RFA) is pivotal in non-surgical hepatocellular carcinoma (HCC) treatments but poses a high postoperative recurrence risk, exceeding conventional surgeries. Insufficient tumor ablation may trigger immune responses, promoting tumor progression locally. Hence, this study seeks to pinpoint immune biomarkers to improve treatment precision and prognostic accuracy for RFA patients.

Methods: The study utilized data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and The International Cancer Genome Consortium (ICGC) database to investigate novel immune biomarkers influencing the prognosis of patients undergoing insufficient radiofrequency ablation (IRFA). Subsequently, an IRFA model was developed and validated. Then, we employed Quantitative real time-Polymerase Chain Reaction (qPCR), Western blotting (WB), immunohistochemistry (IHC), and immunofluorescence (IF) techniques on human HCC cell lines and IRFA animal model to validate ADP-ribosylation factor 4 (ARF4) and Eukaryotic translation initiation factor 5B (EIF5B) expression and prognostic relevance post-IRFA. In addition, knockdown of ARF4 and EIF5B was performed to evaluate cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Finally, transcriptome sequencing was subsequently performed to confirm and extend our findings.

Results: ARF4 and EIF5B were identified as critical immune targets affecting IRFA patient prognosis, forming the basis of an IRFA risk model. High-risk scores in this model correlated with poorer prognoses and reduced responsiveness to immune checkpoint inhibitors (ICIs) across multiple cancer types. Experimental validations confirmed the protective role of ARF4 and EIF5B in IRFA outcomes, while knockdown experiments suggested their involvement in promoting cell proliferation, migration, invasion, and EMT in IRFA models, potentially through pathways like P53 and Transforming Growth Factor Beta(TGF-β) signaling pathway activation as indicated by transcriptome sequencing.

Conclusion: ARF4 and EIF5B have demonstrated promising potential as biomarkers influencing patient prognosis following RFA in HCC. These findings suggest they could serve as viable therapeutic targets aimed at mitigating HCC recurrence post-RFA.

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来源期刊
CiteScore
0.50
自引率
2.40%
发文量
108
审稿时长
16 weeks
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