Wang Hanjun, Wang Ling, Zhang Sheng, Liu Qicai, Gao Feng
Department of Pathology, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350004, People's Republic of China.
Department of Pathology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Cancer Cell Int. 2024 May 19;24(1):175. doi: 10.1186/s12935-024-03362-w.
The incidence and mortality of lung cancer is the highest in China and the world. Brain is the most common distant metastasis site of lung cancer. Its transfer mechanism and predictive biomarkers are still unclear. EZH2 participates in the catalysis of transcriptional inhibition complex, mediates chromatin compactness, leads to the silencing of its downstream target genes, participates in the silencing of multiple tumor suppressor genes, and is related to cell proliferation, apoptosis and cycle regulation. In physiology, EZH2 has high activity in stem cells or progenitor cells, inhibits genes related to cell cycle arrest and promotes self-renewal. To detect the expression and mutation of EZH2 gene in patients with brain metastasis of lung cancer, and provide further theoretical basis for exploring the pathogenesis of brain metastasis of lung cancer and finding reliable biomarkers to predict brain metastasis of lung cancer.
This study investigated susceptible genes for brain metastasis of lung cancer. The second-generation sequencing technology was applied to screen the differential genes of paired samples (brain metastasis tissues, lung cancer tissues and adjacent tissues) of lung cancer patients with brain metastasi.
It revealed that there was a significant difference in the G553C genotype of EZH2 between lung cancer brain metastasis tissues and lung cancer tissues (p = 0.045). The risk of lung cancer brain metastasis in G allele carriers was 2.124 times higher than that in C allele carriers. Immunohistochemistry showed that compared with lung cancer patients and lung cancer patients with brain metastasis, the expression level of EZH2 in lung cancer tissues of lung cancer patients was significantly higher than that in adjacent lung tissues (p < 0.0001), and higher than that in brain metastasis tissues (p = 0.0309). RNA in situ immunohybridization showed that EZH2 mRNA expression was gradually high in lung cancer adjacent tissues, lung cancer tissues and lung cancer brain metastasis tissues.
EZH2 G553C polymorphism contributes to the prediction of brain metastasis of lung cancer, in which G allele carriers are more prone to brain metastasis.
肺癌的发病率和死亡率在我国乃至全球都是最高的。脑是肺癌最常见的远处转移部位。其转移机制及预测性生物标志物仍不明确。EZH2参与转录抑制复合物的催化，介导染色质紧密化，导致其下游靶基因沉默，参与多个肿瘤抑制基因的沉默，并与细胞增殖、凋亡及周期调控相关。在生理状态下，EZH2在干细胞或祖细胞中具有高活性，抑制与细胞周期停滞相关的基因并促进自我更新。检测肺癌脑转移患者EZH2基因的表达及突变情况，为探讨肺癌脑转移的发病机制及寻找预测肺癌脑转移的可靠生物标志物提供进一步的理论依据。
本研究对肺癌脑转移的易感基因进行研究。应用二代测序技术筛选肺癌脑转移患者配对样本（脑转移组织、肺癌组织及癌旁组织）的差异基因。
结果显示，肺癌脑转移组织与肺癌组织中EZH2的G553C基因型存在显著差异（p = 0.045）。G等位基因携带者发生肺癌脑转移的风险是C等位基因携带者的2.124倍。免疫组化显示，与肺癌患者及肺癌脑转移患者相比，肺癌患者肺癌组织中EZH2的表达水平显著高于癌旁肺组织（p < 0.0001），且高于脑转移组织（p = 0.0309）。RNA原位免疫杂交显示，EZH2 mRNA表达在肺癌癌旁组织、肺癌组织及肺癌脑转移组织中呈逐渐升高趋势。
EZH2 G553C多态性有助于预测肺癌脑转移，其中G等位基因携带者更易发生脑转移。
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