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| HSPH1在肝细胞癌中的表达及临床意义 |
| Expression and clinical significance of HSPH1 in hepatocellular carcinoma 、 |
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| DOI：10.3969/j.issn.1007-8134.2023.03.02 |
| 中文关键词: 肝细胞癌 热休克蛋白 HSPH1 生物信息学 癌症基因组图谱 通量基因表达数据库 人类蛋白质图谱数据库 预后 |
| 英文关键词: hepatocellular carcinoma heat shock protein HSPH1 bioinformatics the cancer genome atlas gene expression omnibus human protein atls prognosis |
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| 中文摘要: |
| 目的?基于癌症基因组图谱数据库（The Cancer Genome Atlas, TCGA）、高通量基因表达数据库（Gene Expression Omnibus, GEO）及人类蛋白质图谱数据库（Human Protein Atls, HPA）等生物信息学数据库探讨热休克蛋白H1（heat shock protein H1, HSPH1）在肝细胞癌中的表达及临床意义。方法?下载TCGA和GEO数据库肝细胞癌相关mRNA微阵列表达谱，比较肝细胞癌和癌旁组织的HSPH1 mRNA表达差异，并利用HPA数据库信息验证其蛋白水平的表达。分析HSPH1表达与肝细胞癌患者预后的相关性。建立ROC曲线和列线图模型，比较不同HSPH1表达组患者的生存差异。采用R软件分析HSPH1表达与肝细胞癌组织中免疫细胞浸润、免疫细胞生物标志物和免疫检查点的相关性。采用STRING数据库分析HSPH1相关蛋白质-蛋白质相互作用网络信息。并利用基因本体分析 （Gene Ontology, GO）、京都基因与基因组数据库（Kyoto Encyclopedia of Genes and Genomes, KEGG）和基因集富集分析（Gene Set Enrichment Analysis, GSEA）等数据库分析HSPH1在肝细胞癌中的功能及信号通路。结果?HSPH1在肝细胞癌组织中的表达水平高于癌旁组织（P=0.000），Kaplan-Meier图显示HSPH1高表达肝细胞癌患者的总体生存期（P=0.000）、疾病特异性生存期（P=0.000）和无进展间隔期（P=0.010）均较HSPH1低表达者更短，HSPH1对肝细胞癌具有较好的诊断价值（AUC=0.895，95%CI：0.862～0.928，P=0.000）。多因素Cox回归分析显示，HSPH1是肝细胞癌患者预后的预测因素（HR=2.226，95%CI：1.393～3.557，P=0.000）。时间依赖性ROC曲线图显示1年、3年和5年AUC分别为0.699、0.581、0.588。在肝细胞癌组织中，HSPH1蛋白表达水平与树突状细胞和细胞毒性细胞浸润呈负相关，与巨噬细胞、CD56高表达的NK细胞等免疫细胞浸润及免疫检查点程序性死亡受体1和细胞毒性T淋巴细胞相关蛋白4表达呈弱正相关。蛋白质-蛋白质相互作用、GO、KEGG和GSEA通路富集分析显示HSPH1与HSPA2、HSPA4、HSPA8和HSPA9等分子相互作用，并与HSPA4、HSPA8表达呈正相关，且具有调节凋亡、抗原加工和提呈、调节免疫等功能。结论?HSPH1在肝细胞癌组织中高表达，是肝细胞癌潜在的诊断和预后标志物。HSPH1参与了肝细胞癌的免疫调节过程，可能成为其治疗靶点之一。 |
| 英文摘要: |
| Objective To investigate the expression and clinical significance of HSPH1 in hepatocellular carcinoma (HCC) based on The Cancer Genome Atlas (TCGA), Gene Expression omnibus (GEO) and the Human Protein Atlas (HPA) databases. Methods?The expression profiles of mRNA microarray associated with HCC were downloaded from TCGA and GEO databases. The differences of HSPH1mRNA expression between HCC and adjacent tissues were compared, and the protein level was verified by HPA database. The correlation between the expression of HSPH1 and the prognosis of patients with HCC was analyzed. The receiver operating characteristic (ROC) curve and nomogram model were established, and the survival status of patients with different HSPH1 expression groups were compared. R software was used to analyze the correlation between HSPH1 expression and immune cell infiltration, immune cell biomarker and immune checkpoint in HCC tissue. STRING database was used to analyze the protein-protein interaction network information related to HSPH1. The function and signal pathway of HSPH1 in HCC were analyzed by Gene Ontology Analysis (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA). Results?The expression level of HSPH1 in HCC was higher than that in adjacent tissues. Kaplan-Meier showed that the time of overall survival (P=0.000), disease-specific survival (P=0.000) and progression-free interval (P=0.010) of patients with high expression of HSPH1 were shorter than those with low expression of HSPH1. HSPH1 had a good diagnostic value for HCC (AUC=0.895, 95%CI: 0.862～0.928, P=0.000). Multivariate Cox regression analysis showed that HSPH1 was a predictor of prognosis in patients with HCC (HR=2.226, 95%CI: 1.393～3.557, P=0.000). Time-dependent ROC analysis showed that the area under curve (AUC) of 1 year, 3 years and 5 years were 0.699, 0.581 and 0.588, respectively. In HCC, the expression of HSPH1 protein was negatively correlated with the infiltration of dendritic cells and cytotoxic cells, and weakly positively correlated with the infiltration of immune cells such as macrophages and NK cells with high expression of CD56, and the expression of programmed death 1 and cytotoxic T lymphocyte-associated protein 4 at immune checkpoints. Protein-protein interaction, GO, KEGG and GSEA pathway enrichment analysis showed that HSPH1 interacted with HSPA2, HSPA4, HSPA8 and HSPA9, and positively correlated with the expression of HSPA4 and HSPA8, and had the functions of regulating apoptosis, antigen processing and presentation, and regulating immunity. Conclusions?HSPH1 is highly expressed in HCC and is a potential diagnostic and prognostic marker of HCC. HSPH1 is involved in the immune regulation of HCC and may be one of its therapeutic targets. |
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