Huang Zhendong, Liu Zhendong, Cheng Xingbo, Han Zhibin, Li Jiwei, Xia Tian, Gao Yanzheng, Wei Li
Department of Thoracic Surgery, Zhengzhou Key Laboratory for Surgical Treatment for End-Stage Lung Disease, Zhengzhou University People's Hospital, Henan Provincial People's Hospital, Zhengzhou, China.
Department of Surgery of Spine and Spinal Cord, Henan Provincial People's Hospital, Henan International Joint Laboratory of Intelligentized Orthopedics Innovation and Transformation, Henan Key Laboratory for Intelligent Precision Orthopedics, Zhengzhou University People's Hospital, People's Hospital of Henan University, Zhengzhou, China.
Ann Transl Med. 2021 Oct;9(20):1559. doi: 10.21037/atm-21-4935.
Recent studies have demonstrated that upregulation of heat shock transcription factor 2 binding protein (HSF2BP) may promote genomic instability, thereby leading to the development of tumors and also providing a potential target for biological antitumor therapy. However, the role of HSF2BP has so far remained unclear in lung adenocarcinoma (LUAD).
To explore the function of HSF2BP in LUAD, we collected transcriptome data for 551 lung samples from The Cancer Genome Atlas (TCGA) database and methylation data for 461 lung samples from the University of California Santa Cruz (UCSC) genome database, in addition to corresponding clinical information. We used bioinformatic approaches to systematically explore the role of HSF2BP in LUAD, including Gene Set Enrichment Analysis (GSEA), coexpression analysis, the Tumor IMmune Estimation Resource (TIMER) tool, Connectivity Map (CMap) analysis, and a meta-analysis involving three Gene Expression Omnibus (GEO) datasets and one TCGA dataset.
Our results found that upregulation of HSF2BP in LUAD was an independent risk factor for the prognosis and diagnosis of LUAD. GSEA analysis showed HSF2BP expression was associated with vital signaling pathways, including the cell cycle, P53 signaling pathway, and homologous recombination. Coexpression analysis revealed 10 HSF2BP-associated genes, including oncogenes and tumor suppressor genes. Additionally, we found that HSF2BP expression was negatively correlated with B-cell infiltration and had a potential interaction with CD80 in LUAD, which may play an important role in tumor immune escape. Finally, we identified four small-molecule drugs which show promise for LUAD treatment.
The present study found that elevated HSF2BP posed a threat to prognosis in LUAD patients. HSF2BP might have been involved in tumorigenesis by influencing genomic stability and contributing to tumor immune evasion in the tumor immune microenvironment of LUAD. These findings suggest that HSF2BP may provide a vulnerable target for improving and enhancing treatment of LUAD.
最近的研究表明，热休克转录因子2结合蛋白（HSF2BP）的上调可能促进基因组不稳定，从而导致肿瘤的发生，也为生物抗肿瘤治疗提供了一个潜在靶点。然而，HSF2BP在肺腺癌（LUAD）中的作用迄今为止仍不清楚。
为了探究HSF2BP在LUAD中的功能，我们从癌症基因组图谱（TCGA）数据库收集了551个肺样本的转录组数据，从加利福尼亚大学圣克鲁兹分校（UCSC）基因组数据库收集了461个肺样本的甲基化数据，以及相应的临床信息。我们使用生物信息学方法系统地探究HSF2BP在LUAD中的作用，包括基因集富集分析（GSEA）、共表达分析、肿瘤免疫估计资源（TIMER）工具、连接图谱（CMap）分析，以及一项涉及三个基因表达综合数据库（GEO）数据集和一个TCGA数据集的荟萃分析。
我们的结果发现，LUAD中HSF2BP的上调是LUAD预后和诊断的独立危险因素。GSEA分析表明，HSF2BP表达与重要信号通路相关，包括细胞周期、P53信号通路和同源重组。共表达分析揭示了10个与HSF2BP相关的基因，包括癌基因和肿瘤抑制基因。此外，我们发现HSF2BP表达与B细胞浸润呈负相关，并且在LUAD中与CD80存在潜在相互作用，这可能在肿瘤免疫逃逸中起重要作用。最后，我们确定了四种对LUAD治疗有前景的小分子药物。
本研究发现，HSF2BP升高对LUAD患者的预后构成威胁。HSF2BP可能通过影响基因组稳定性并在LUAD的肿瘤免疫微环境中促进肿瘤免疫逃逸而参与肿瘤发生。这些发现表明，HSF2BP可能为改善和加强LUAD治疗提供一个脆弱靶点。
