Department of Hepatobiliary and Pancreatic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China.
Int J Mol Sci. 2023 Jan 31;24(3):2653. doi: 10.3390/ijms24032653.
Complex immune contexture leads to resistance to immunotherapy in hepatocellular carcinoma (HCC), and the need for new potential biomarkers of immunotherapy in HCC is urgent. Histone chaperones are vital determinants of gene expression and genome stability that regulate tumor development. This study aimed to investigate the effect of histone chaperones on tumor immunity in HCC. Bioinformatics analyses were initially performed using The Cancer Genome Atlas (TCGA) database, and were validated using the Gene Expression Omnibus (GEO) database and the International Cancer Genome Consortium (ICGC) database. Immune-related histone chaperones were screened with the Spearman rank coefficient. Consensus clustering was utilized to divide the HCC samples into two clusters. ESTIMATE, CIBERSORT and ssGSEA analyses were performed to assess immune infiltration. The expression of immunomodulatory genes, chemokines and chemokine receptors was analyzed to evaluate sensitivity to immunotherapy. The differentially expressed genes (DEGs) were included in weighted gene coexpression network analysis (WGCNA) to identify the hub genes. Enrichment analyses were used to investigate the functions of the hub genes. The Kaplan-Meier method and log-rank test were conducted to draw survival curves. A Cox regression analysis was utilized to identify independent risk factors affecting prognosis. and were screened out from 36 known histone chaperones based on their strongest correlation with the ESTIMATE score. Cluster 2, with high expression and low expression, tended to have stronger immune infiltration and better sensitivity to immunotherapy than Cluster 1, with low expression and high expression. Furthermore, WGCNA identified 12 hub genes closely correlated with immune infiltration from the DEGs of the two clusters, of which was proven to be an independent protective factor of HCC patients. and are expected to be biomarkers for precisely predicting the effect of immunotherapy, and is expected to be a therapeutic target of HCC.
复杂的免疫结构导致肝癌（HCC）对免疫治疗产生耐药性，因此迫切需要新的 HCC 免疫治疗潜在生物标志物。组蛋白伴侣是决定基因表达和基因组稳定性的重要因素，可调节肿瘤的发展。本研究旨在探讨组蛋白伴侣对 HCC 肿瘤免疫的影响。首先使用癌症基因组图谱（TCGA）数据库进行生物信息学分析，并使用基因表达综合数据库（GEO）数据库和国际癌症基因组联盟（ICGC）数据库进行验证。使用 Spearman 秩相关系数筛选与肿瘤免疫相关的组蛋白伴侣。采用共识聚类将 HCC 样本分为两个亚群。采用 ESTIMATE、CIBERSORT 和 ssGSEA 分析评估免疫浸润。分析免疫调节基因、趋化因子和趋化因子受体的表达，以评估对免疫治疗的敏感性。将差异表达基因（DEGs）纳入加权基因共表达网络分析（WGCNA），以鉴定枢纽基因。采用富集分析探讨枢纽基因的功能。采用 Kaplan-Meier 方法和对数秩检验绘制生存曲线。采用 Cox 回归分析鉴定影响预后的独立危险因素。根据与 ESTIMATE 评分的相关性，从 36 种已知的组蛋白伴侣中筛选出与免疫相关的 和 。与 表达低和 表达高的 Cluster 1 相比，Cluster 2 中 表达高和 表达低，其免疫浸润更强，对免疫治疗的敏感性更高。此外，从两个聚类的 DEGs 中，WGCNA 鉴定出 12 个与免疫浸润密切相关的枢纽基因，其中 被证明是 HCC 患者的独立保护因素。 和 有望成为精确预测免疫治疗效果的生物标志物，而 有望成为 HCC 的治疗靶点。
