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ANP32 家族作为与肝癌免疫浸润相关的诊断、预后和治疗性生物标志物。

ANP32 Family as Diagnostic, Prognostic, and Therapeutic Biomarker Related to Immune Infiltrates in Hepatocellular Carcinoma.

机构信息

Department of General Surgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

Key Laboratory of Hepatosplenic Surgery, Ministry of Education, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.

出版信息

Dis Markers. 2022 Mar 3;2022:5791471. doi: 10.1155/2022/5791471. eCollection 2022.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide, with high incidence and mortality rate. There is an urgent need to identify effective diagnostic and prognostic biomarkers for HCC. Members of the acidic leucine-rich nucleophosphoprotein 32 (ANP32) family, which mainly includes , , and , are abnormally expressed and have prognostic value in certain cancers. However, the diagnostic, prognostic, and therapeutic value of ANP32 family members in HCC has not yet been fully studied. In this study, we identified the diagnostic and prognostic value of ANP32 family members in HCC. Transcriptome data from public databases, such as the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, suggested that , , and were upregulated in HCC tissues, and high expression of ANP32 family members was associated with advanced pathologic stage and histologic grade. Our immunohistochemistry and western blot results further verified the differential expression of ANP32 family members. , , and had an outstanding diagnostic potential. Survival analysis of HCC patients in TCGA databases demonstrated that , , and were associated with poor overall survival (OS) and disease-specific survival (DSS). Univariate and multivariate Cox analyses suggested the capability of and to independently predict the OS and DSS of HCC patients. Gene set enrichment analysis (GSEA) showed that ANP32 family members were associated with immune response, epidermal cell differentiation, and stem cell proliferation. Expression of ANP32 family members was associated with immune cell infiltration and immune status in the tumor microenvironment of HCC, and patients with high ANP32 family expression had poor sensitivity to immunotherapy. Finally, we identified potential chemotherapy drugs for HCC patients with high ANP32 family expression by CellMiner database. This study suggested the diagnostic, prognostic, and therapeutic roles of the ANP32 family in HCC patients, providing potential therapeutic targets for HCC.

摘要

肝细胞癌(HCC)是全球最常见的肿瘤之一,发病率和死亡率都很高。迫切需要发现有效的 HCC 诊断和预后生物标志物。酸性亮氨酸丰富核磷蛋白 32(ANP32)家族成员主要包括 、 、 和 ,它们在某些癌症中异常表达并具有预后价值。然而,ANP32 家族成员在 HCC 中的诊断、预后和治疗价值尚未得到充分研究。在这项研究中,我们确定了 ANP32 家族成员在 HCC 中的诊断和预后价值。来自公共数据库(如癌症基因组图谱(TCGA)和基因型组织表达(GTEx)数据库)的转录组数据表明, 、 、 和 在 HCC 组织中上调,并且 ANP32 家族成员的高表达与晚期病理分期和组织学分级相关。我们的免疫组织化学和 Western blot 结果进一步验证了 ANP32 家族成员的差异表达。 、 、 和 具有出色的诊断潜力。TCGA 数据库中 HCC 患者的生存分析表明, 、 、 和 与总生存期(OS)和疾病特异性生存期(DSS)不良相关。单因素和多因素 Cox 分析表明 和 能够独立预测 HCC 患者的 OS 和 DSS。基因集富集分析(GSEA)表明 ANP32 家族成员与免疫反应、表皮细胞分化和干细胞增殖有关。ANP32 家族成员的表达与 HCC 肿瘤微环境中免疫细胞浸润和免疫状态相关,并且表达高 ANP32 家族的患者对免疫治疗的敏感性较差。最后,我们通过 CellMiner 数据库确定了具有高 ANP32 家族表达的 HCC 患者潜在的化疗药物。这项研究表明 ANP32 家族在 HCC 患者中的诊断、预后和治疗作用,为 HCC 提供了潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f56/8913125/f329a40d6fba/DM2022-5791471.001.jpg

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