Exploration of YBX1 role in the prognostic value and immune characteristics by single-cell and bulk sequencing analysis for liver hepatocellular carcinoma

IF 3.2 4区医学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Journal of Gene Medicine Pub Date : 2024-03-06 DOI:10.1002/jgm.3680

Qingqing Zhang, Bingye Zhu, Hongyan Yang, Fei Li, Ying Qu, Lungen Lu, Qidi Zhang

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引用次数: 0

Abstract

Background

Y-box binding protein 1 (YBX1) plays a variety of roles in progression of multiple tumors. However, the role of YBX1 in prognostic value and immune regulation for liver hepatocellular carcinoma (LIHC) remains unclear. The present study aimed to examine the effect of YBX1 on the regulation of tumor immunity and survival prediction in LIHC patients.

Methods

YBX1-related expression profiles and single-cell and bulk sequencing analysis were performed using online databases. YBX1 expression was validated by a quantitative real-time PCR (qRT-PCR), western blotting and immunohistochemistry. Univariate/multivariate Cox regression analysis was performed to determine independent predictors of overall survival (OS). The ESTIMATE (i.e., Estimation of STromal and Immune cells in MAlignant Tumor tissues using Expression data) algorithm and Tumor Immune Dysfunction and Exclusion (TIDE) analysis were used to assess the relationships between YBX1 and LIHC immunity.

Results

YBX1 was over-expressed in LIHC tissues and cell lines. High YBX1 expression was significantly associated with poor OS. Univariate/multivariate Cox regression analysis revealed that YBX1 was an independent prognostic factor for LIHC. Gene set enrichment analysis revealed that YBX1 was associated with multiple signaling pathways correlated to LIHC. Additionally, YBX1 was expressed in multiple immune cells and was significantly correlated with immune cells, immune checkpoint markers and tumor immune microenvironment. The TIDE analysis demonstrated that LIHC patients with high YBX1 expression showed a higher T-cell dysfunction score and a higher exclusion score, as well as poorer immunotherapy response.

Conclusions

YBX1 plays crucial oncogenic roles in LIHC and is closely associated with the immune defense system. YBX1 inhibition may serve as a potential treatment for LIHC.

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通过单细胞和批量测序分析探讨 YBX1 在肝肝细胞癌预后价值和免疫特征中的作用

背景：Y-盒结合蛋白 1（YBX1Y-box 结合蛋白 1（YBX1）在多种肿瘤的进展过程中发挥着多种作用。然而，YBX1在肝肝细胞癌（LIHC）的预后价值和免疫调节中的作用仍不清楚。本研究旨在探讨YBX1对LIHC患者肿瘤免疫调节和生存预测的影响：方法：利用在线数据库进行YBX1相关表达谱分析以及单细胞和批量测序分析。YBX1的表达通过定量实时PCR（qRT-PCR）、免疫印迹和免疫组化进行了验证。进行了单变量/多变量Cox回归分析，以确定总生存期（OS）的独立预测因素。ESTIMATE（即利用表达数据估算恶性肿瘤组织中的STromal和免疫细胞）算法和肿瘤免疫功能障碍与排斥（TIDE）分析用于评估YBX1与LIHC免疫之间的关系：结果：YBX1在LIHC组织和细胞系中过度表达。YBX1的高表达与不良OS显著相关。单变量/多变量 Cox 回归分析显示，YBX1 是 LIHC 的独立预后因素。基因组富集分析显示，YBX1与多种与LIHC相关的信号通路有关。此外，YBX1在多种免疫细胞中表达，并与免疫细胞、免疫检查点标记物和肿瘤免疫微环境显著相关。TIDE分析表明，YBX1高表达的LIHC患者表现出更高的T细胞功能障碍评分和更高的排斥评分，以及更差的免疫治疗反应：结论：YBX1在LIHC中发挥着关键的致癌作用，并与免疫防御系统密切相关。结论：YBX1在LIHC中起着关键的致癌作用，并与免疫防御系统密切相关，抑制YBX1可作为治疗LIHC的一种潜在方法。

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.