| Daijun Xing,Fuman Wang,Min Qi,Xiaokun Wang,Xu Zhu,Yufeng Cao,Zhengtong Zhao,Gaoyang Lin. EZH2 is a biomarker associated with lung cancer diagnosis and immune infiltrates without prognostic specificity: a study based on the cancer genome atlas data. Oncol Transl Med, 2023, 9: 99-114. |
| EZH2是一种与肺癌诊断和免疫浸润相关的无预后特异性的生物标志物：一项基于癌症基因组图谱数据的研究 |
| EZH2 is a biomarker associated with lung cancer diagnosis and immune infiltrates without prognostic specificity: a study based on the cancer genome atlas data |
| Received:October 10, 2022 Revised:May 29, 2023 |
| DOI：10.1007/s10330-022-0599-9 |
| 中文关键词: EZH2，肺癌，诊断，预后，免疫浸润 |
| 英文关键词: Enhancer of zeste homolog 2; lung cancer; diagnosis; prognosis; immune infiltrating |
| 基金项目: |
| Author Name | Affiliation | E-mail | | Daijun Xing | Cardiac Center (Department of Vascular Surgery), The Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao 266033, China | | | Fuman Wang | Cardiac Center (Department of Vascular Surgery), The Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao 266033, China | | | Min Qi | Cardiac Center (Department of Vascular Surgery), The Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao 266033, China | | | Xiaokun Wang | Cardiac Center (Department of Vascular Surgery), The Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao 266033, China | | | Xu Zhu | Cardiac Center (Department of Vascular Surgery), The Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao 266033, China | | | Yufeng Cao | Cardiac Center (Department of Vascular Surgery), The Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao 266033, China | | | Zhengtong Zhao | Cardiac Center (Department of Vascular Surgery), The Affiliated Qingdao Hiser Hospital of Qingdao University (Qingdao Hospital of Traditional Chinese Medicine), Qingdao 266033, China | | | Gaoyang Lin* | Department of Thoracic Surgery, The Affiliated Qingdao Hiser Medical Center of Qingdao University Medical College | lingaoyang1988@126.com |
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| 中文摘要: |
| zeste基因增强子同源物2 (EZH2)是多梳抑制复合物2 (PRC2)的催化亚基。EZH2的失调可引起基因表达和功能的改变，从而促进癌症的发生发展。最近的研究表明，EZH2在NSCLC患者中具有潜在的预后作用。然而，EZH2表达水平在NSCLC中的预后价值存在争议。本研究基于癌症基因组图谱(the cancer Genome Atlas, TCGA)数据库，评估ezh2在肺癌(LC-LUAD/ LUSC)中的预后价值。采用Kruskal-Wallis检验、Wilcoxon符号秩和检验和logistic回归分析EZH2表达与临床病理特征的关系。采用Cox回归和Kaplan-Meier法评估预后相关因素。采用基因集富集分析(GSEA)确定与EZH2相关的关键通路。通过单样本基因集富集分析(ssGSEA)探讨EZH2与肿瘤免疫浸润的相关性。在多个LC队列中，EZH2在肿瘤组织中随着扩增而上调。EZH2高表达与较差的总生存期(OS)相关。GSEA提示EZH2调节固有免疫系统、细胞外基质、基质体、表面活性物质代谢。ssGSEA结果显示EZH2表达水平与Th2细胞浸润水平呈正相关，与肥大细胞浸润水平呈显著负相关。EZH2与肺癌免疫浸润相关，在肺癌中显著高表达，其诊断价值优于预后，为进一步研究EZH2在肺癌中的免疫调节作用奠定了基础。 |
| 英文摘要: |
| Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of polycomb repressive complex 2 (PRC2).
Dysregulation of EZH2 causes alteration of gene expression and functions, thereby promoting cancer
development. Recent studies suggest that EZH2 has a potential prognostic role in patients with nonsmall cell lung cancer (NSCLC). However, the prognostic value of EZH2 expression levels in NSCLC is
controversial. In this study, we evaluated the prognostic value in lung cancer (LC-LUAD/LUSC) based on
data from The Cancer Genome Atlas (TCGA) database. Kruskal-Wallis test, Wilcoxon signed-rank test, and
logistic regression were used to evaluate the relationship between EZH2 expression and clinicopathological
features. Cox regression and the Kaplan-Meier method were adopted to evaluate prognosis-related factors.
Gene set enrichment analysis (GSEA) was performed to identify the key pathways related to EZH2. The
correlations between EZH2 and cancer immune infiltrates were investigated by single-sample Gene Set
Enrichment Analysis (ssGSEA). EZH2 was found to be up regulated with amplification in tumor tissues
in multiple LC cohorts. High EZH2 expression was associated with poorer overall survival (OS). GSEA
suggested that EZH2 regulates innate immune system, ECM affiliated, matrisome, surfactant metabolism.
Notably, ssGSEA indicated that EZH2 expression was positively correlated with infiltrating levels of Th2
cells and significantly negatively correlated with mast cell infiltration level. These results suggest that EZH2
is associated with LC immune infiltration and significantly over-expressed in lung cancer, and its diagnostic
value is better than prognosis, which lays a foundation for further study of the immunomodulatory role of
EZH2 in LC. |
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