HSP90AA1 是肝细胞癌的一个不利预后因素，并导致肿瘤发生和化疗耐药。

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2024-10-10 DOI:10.1016/j.tranon.2024.102148

Zhaoying Wang , Longfei Fan , Heng Xu , Zhongqiang Qin , Ziyi Zhu , Di Wu , Yigang Zhang , Ruoyu Liu , Jianzhu Wei , Zhen Qian , Peipei Yang , Bo Xie , Mu Yuan , Jingyu Qian

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引用次数: 0

摘要

肝细胞癌（HCC）仍然是导致肿瘤相关死亡的主要原因之一。越来越多的证据表明，免疫性细胞死亡（ICD）可能发生在肿瘤细胞中。然而，在 HCC 中与 ICD 相关的研究还很有限。本研究从癌症基因组图谱（Cancer Genome Atlas）、国际癌症基因组联盟（International Cancer Genome Consortium）和基因表达总库（Gene Expression Omnibus）数据库中收集了 HCC RNA 测序数据。使用 R 软件分析 ICD 在 HCC 中的表达，并筛选出具有预后价值的重要基因。采用细胞活力检测、克隆形成检测和活/死染色检测来确定基因的功能。在对差异表达基因（DEGs）和ICD相关基因（ICDRGs）进行交叉分析后，发现了7个在HCC中差异表达的ICDRGs。其中，HSP90AA1 在 HCC 中的预后价值最高，其表达也在公共队列、细胞系和临床组织样本中得到了验证。HSP90AA1 的高表达表明 HCC 的预后较差，而 HSP90AA1 的敲除能显著抑制 HCC 的细胞活力和化疗耐药性。ICD相关基因HSP90AA1是HCC的不利因素，HSP90AA1的高表达导致肿瘤细胞存活和化疗耐药。

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HSP90AA1 is an unfavorable prognostic factor for hepatocellular carcinoma and contributes to tumorigenesis and chemotherapy resistance

Hepatocellular carcinoma (HCC) is still one of the leading causes of tumor-related deaths. Accumulating evidence indicates that immunogenic cell death (ICD) could occur in tumor cells. However, ICD-related studies are limited in HCC. This study collected HCC RNA sequencing data from the Cancer Genome Atlas, International Cancer Genome Consortium, and Gene Expression Omnibus databases. R software was used to analyze the expression of ICD in HCC and to screen essential genes with prognostic value. qRT-PCR and WB determined the mRNA and protein expressions of hub gene. Cell viability assay, Clonal formation assay, and Live/dead staining assay were employed to determine the gene functions. After cross-analysis of differentially expressed genes (DEGs) and ICD-related genes (ICDRGs), 7 differentially expressed ICDRGs were identified in HCC. Of them, HSP90AA1, with the most excellent prognostic value in HCC, was selected, whose expression was also validated in public cohorts, cell lines, and clinical tissue samples. High HSP90AA1 expression indicated an inferior prognosis of HCC, and HSP90AA1 knockdown significantly suppressed cell viability and chemotherapy resistance of HCC. ICD-related gene HSP90AA1 was an unfavorable factor for HCC, and high HSP90AA1 expression contributed to tumor cell survival and chemotherapy resistance.

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来源期刊

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.