Comprehensive Analysis of the Role of Heat Shock Proteins in the Immune Microenvironment and Clinical Significance of Hepatocellular Carcinoma.

IF 4.2 3区 医学 Q2 ONCOLOGY
Journal of Hepatocellular Carcinoma Pub Date : 2025-02-17 eCollection Date: 2025-01-01 DOI:10.2147/JHC.S495151
Han Xiao, Ben Wang, Shaomin Xiong, Chunbo Li, Yanbao Ding, Dai Chao, Baohua Mei, Naiying Shen, Gang Luo
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Abstract

Purpose: Hepatocellular carcinoma (HCC) is a prevalent malignancy that not only imposes a substantial financial burden but also significantly impacts the quality of life and overall survival of affected individuals. Heat shock proteins (HSPs) are a protein class with significant involvement in safeguarding and restoring cellular integrity. They help restore proper protein structure by binding to and refolding denatured proteins. However, the specific role of HSPs in HCC requires further investigation.

Methods: We analyzed the genomic characteristics of HSPs in liver cancer in the TCGA and ICGC databases, and functional enriched analysis of HSPs. Construction of an HSPs-Related Prognostic Model for patients with hepatocellular carcinoma. HSP-related risk score (HRRS) was identified as an independent prognostic factor in patients with hepatocellular carcinoma, and the clinical pathological characteristics and immune microenvironment of high-risk and low-risk groups were compared. Further, we studied HRRS-based liver cancer treatment strategies and confirmed the protein expression of HSPD1 and DNAJC5 in normal liver tissues and hepatocellular carcinoma tissues by collecting human hepatocellular carcinoma tissues.

Results: We observed elevated expression levels of most HSPs across HCC tissues. In addition, 14 hSPs were found to be related to prognostic significance among HCC patients and utilized to develop HRRS prognostic model for prognosis prediction and risk stratification. The prognostic and immunotherapeutic response predictive value of HRRS was validated utilizing data from TCGA and GEO cohorts. Moreover, we created a nomogram to assess HRRS clinical utility and verified its efficiency through various methods. Through IHC was found that HSPD1 and DNAJC5 were significantly overexpressed in hepatocellular carcinoma tissues.

Conclusion: Our results lead us to conclude that HCC's development and progression are intimately associated with HSPs, and the HRRS model represents a potentially robust prognostic model that could assist in clinical decision-making regarding chemotherapy and immunotherapy for HCC patients. Moreover, HSPD1 and DNAJC5 have the potential to serve as therapeutic targets for HCC.

热休克蛋白在肝细胞癌免疫微环境中的作用及临床意义
目的:肝细胞癌(HCC)是一种普遍存在的恶性肿瘤,不仅给患者带来巨大的经济负担,而且显著影响患者的生活质量和总体生存率。热休克蛋白(HSPs)是一类在保护和恢复细胞完整性中起重要作用的蛋白。它们通过结合和重新折叠变性蛋白质来帮助恢复适当的蛋白质结构。然而,热休克蛋白在HCC中的具体作用有待进一步研究。方法:分析TCGA和ICGC数据库中肝癌HSPs的基因组特征,并对HSPs进行功能富集分析。肝细胞癌患者热休克蛋白相关预后模型的建立将热休克蛋白相关风险评分(HRRS)确定为肝细胞癌患者的独立预后因素,并比较高危组和低危组的临床病理特征和免疫微环境。我们进一步研究了基于hrrs的肝癌治疗策略,并通过采集人肝细胞癌组织,证实HSPD1和DNAJC5蛋白在正常肝组织和肝细胞癌组织中的表达。结果:我们观察到大多数HSPs在HCC组织中的表达水平升高。此外,发现14个hSPs与HCC患者预后相关,并利用其建立HRRS预后模型进行预后预测和风险分层。利用TCGA和GEO队列的数据验证了HRRS的预后和免疫治疗反应预测价值。此外,我们创建了一个nomogram来评估HRRS的临床效用,并通过各种方法验证其有效性。通过免疫组化发现HSPD1和DNAJC5在肝细胞癌组织中显著过表达。结论:我们的研究结果使我们得出这样的结论:HCC的发生和进展与HSPs密切相关,HRRS模型代表了一个潜在的强大的预后模型,可以帮助HCC患者的化疗和免疫治疗的临床决策。此外,HSPD1和DNAJC5有可能作为HCC的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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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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