Identification and characterization of RAC1-related immune and prognostic subtypes of hepatocellular carcinoma

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Gene Medicine Pub Date : 2024-07-09 DOI:10.1002/jgm.3719

Wei Wang, Hui Xia, Pei Feng, Bin Dai

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引用次数: 0

Abstract

Background

Hepatocellular carcinoma (HCC) is a malignant tumor with significant variability in prognosis among patients. Ras-related C3 botulinum toxin substrate 1 (RAC1) is a key focus in the area of cancer research. However, the molecular mechanisms of RAC1 in HCC remain incompletely elucidated.

Materials and methods

In this study, bioinformatics analysis was used, and public databases were used to obtain information about HCC cases. The samples were categorized into two groups of high and low expression based on the expression level of RAC1 gene. The limma package was used to calculate the differentially expressed genes between the two groups, and univariate Cox regression analysis was used to screen the prognostic related factors. Consensus clustering analysis was performed using the ConsensusClusterPlus package to identify molecular subtypes of HCC patients. Immune cell infiltration and ESTIMATE scores were assessed using the single sample gene set enrichment analysis and ESTIMATE algorithms. The sensitivity of different isoforms to chemotherapeutic agents was predicted by the oncoPredict package. Finally, we also performed cell function experiments to validate the biological role of RAC1 in vitro. Initially, we classified patients into high and low expression groups based on RAC1 gene expression levels and identified 195 up-regulated genes and 107 down-regulated genes. Through univariate Cox regression analysis, we screened out 169 prognosis-related factors. Furthermore, HCC patients were categorized into two subtypes. Subsequently, Kaplan–Meier survival curves showed that there was a significant difference in prognosis between the two molecular subtypes. Further analysis indicated substantial differences in gene expression levels and TIDE scores between two molecular subtypes. Moreover, these two subtypes exhibited varying sensitivity to chemotherapy drugs, as evidenced by differences in IC₅₀ values. In addition, we found that the silence of RAC1 could effectively inhibit the migration and invasion of HCC cells in vitro.

Conclusion

This study sheds light on the molecular intricacies of RAC1 in HCC and identifies patient populations that may benefit from immunotherapeutic interventions, with potential implications for tailored treatment strategies.

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肝细胞癌 RAC1 相关免疫亚型和预后亚型的鉴定与特征描述。

背景：肝细胞癌（HCC）是一种恶性肿瘤，不同患者的预后差异很大。Ras 相关 C3 肉毒毒素底物 1（RAC1）是癌症研究领域的一个重点。然而，RAC1在HCC中的分子机制仍未完全阐明：本研究采用生物信息学分析方法，并利用公共数据库获取有关 HCC 病例的信息。根据 RAC1 基因的表达水平，将样本分为高表达和低表达两组。使用 limma 软件包计算两组间差异表达的基因，并使用单变量 Cox 回归分析筛选预后相关因素。使用ConsensusClusterPlus软件包进行共识聚类分析，以确定HCC患者的分子亚型。利用单样本基因组富集分析和ESTIMATE算法评估了免疫细胞浸润和ESTIMATE评分。oncoPredict软件包预测了不同异构体对化疗药物的敏感性。最后，我们还进行了细胞功能实验，以验证 RAC1 在体外的生物学作用。最初，我们根据 RAC1 基因的表达水平将患者分为高表达组和低表达组，并确定了 195 个上调基因和 107 个下调基因。通过单变量 Cox 回归分析，我们筛选出了 169 个与预后相关的因素。此外，我们还将 HCC 患者分为两个亚型。随后，Kaplan-Meier 生存曲线显示，两种分子亚型的预后存在显著差异。进一步的分析表明，两种分子亚型的基因表达水平和 TIDE 评分存在很大差异。此外，这两种亚型对化疗药物的敏感性也不尽相同，IC50 值的差异就证明了这一点。此外，我们还发现沉默 RAC1 能有效抑制 HCC 细胞在体外的迁移和侵袭：本研究揭示了 RAC1 在 HCC 中的分子复杂性，并确定了可能从免疫治疗干预中获益的患者群体，这对定制治疗策略具有潜在的意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Gene Medicine 医学-生物工程与应用微生物

CiteScore

6.40

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： The aims and scope of The Journal of Gene Medicine include cutting-edge science of gene transfer and its applications in gene and cell therapy, genome editing with precision nucleases, epigenetic modifications of host genome by small molecules, siRNA, microRNA and other noncoding RNAs as therapeutic gene-modulating agents or targets, biomarkers for precision medicine, and gene-based prognostic/diagnostic studies. Key areas of interest are the design of novel synthetic and viral vectors, novel therapeutic nucleic acids such as mRNA, modified microRNAs and siRNAs, antagomirs, aptamers, antisense and exon-skipping agents, refined genome editing tools using nucleic acid /protein combinations, physically or biologically targeted delivery and gene modulation, ex vivo or in vivo pharmacological studies including animal models, and human clinical trials. Papers presenting research into the mechanisms underlying transfer and action of gene medicines, the application of the new technologies for stem cell modification or nucleic acid based vaccines, the identification of new genetic or epigenetic variations as biomarkers to direct precision medicine, and the preclinical/clinical development of gene/expression signatures indicative of diagnosis or predictive of prognosis are also encouraged.