EMP3 作为一种预后生物标志物与 GBM 中的 EMT 相关。
EMP3 as a prognostic biomarker correlates with EMT in GBM.
机构信息
Department of Oncology, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.
Department of Oncology, The Beidahuang Group General Hospital, Harbin, 150006, China.
出版信息
BMC Cancer. 2024 Jan 17;24(1):89. doi: 10.1186/s12885-023-11796-0.
BACKGROUND
Glioblastoma (GBM) is the most aggressive malignant central nervous system tumor with a poor prognosis.The malignant transformation of glioma cells via epithelial-mesenchymal transition (EMT) has been observed as a main obstacle for glioblastoma treatment. Epithelial membrane protein 3 (EMP3) is significantly associated with the malignancy of GBM and the prognosis of patients. Therefore, exploring the possible mechanisms by which EMP3 promotes the growth of GBM has important implications for the treatment of GBM.
METHODS
We performed enrichment and correlation analysis in 5 single-cell RNA sequencing datasets. Differential expression of EMP3 in gliomas, Kaplan-Meier survival curves, diagnostic accuracy and prognostic prediction were analyzed by bioinformatics in the China Glioma Genome Atlas (CGGA) database and The Cancer Genome Atlas (TCGA) database. EMP3-silenced U87 and U251 cell lines were obtained by transient transfection with siRNA. The effect of EMP3 on glioblastoma proliferation was examined using the CCK-8 assay. Transwell migration assay and wound healing assay were used to assess the effect of EMP3 on glioblastoma migration. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were used to detect the mRNA and protein expression levels of EMT-related transcription factors and mesenchymal markers.
RESULTS
EMP3 is a EMT associated gene in multiple types of malignant cancer and in high-grade glioblastoma. EMP3 is enriched in high-grade gliomas and isocitrate dehydrogenase (IDH) wild-type gliomas.EMP3 can be used as a specific biomarker for diagnosing glioma patients. It is also an independent prognostic factor for glioma patients' overall survival (OS). In addition, silencing EMP3 reduces the proliferation and migration of glioblastoma cells. Mechanistically, EMP3 enhances the malignant potential of tumor cells by promoting EMT.
CONCLUSION
EMP3 promotes the proliferation and migration of GBM cells, and the mechanism may be related to EMP3 promoting the EMT process in GBM; EMP3 may be an independent prognostic factor in GBM.
背景
胶质母细胞瘤（GBM）是最具侵袭性的恶性中枢神经系统肿瘤，预后不良。上皮-间充质转化（EMT）导致的胶质瘤细胞恶性转化已被视为 GBM 治疗的主要障碍。上皮膜蛋白 3（EMP3）与 GBM 的恶性程度和患者的预后显著相关。因此，探索 EMP3 促进 GBM 生长的可能机制对 GBM 的治疗具有重要意义。
方法
我们在 5 个单细胞 RNA 测序数据集上进行了富集和相关性分析。通过生物信息学分析中国脑胶质瘤基因组图谱（CGGA）数据库和癌症基因组图谱（TCGA）数据库，对 EMP3 在脑胶质瘤中的差异表达、Kaplan-Meier 生存曲线、诊断准确性和预后预测进行分析。通过瞬时转染 siRNA 获得 EMP3 沉默的 U87 和 U251 细胞系。使用 CCK-8 测定法检测 EMP3 对胶质母细胞瘤增殖的影响。通过 Transwell 迁移实验和划痕愈合实验评估 EMP3 对胶质母细胞瘤迁移的影响。最后，采用实时定量聚合酶链反应（qRT-PCR）和 Western blot 检测 EMT 相关转录因子和间充质标志物的 mRNA 和蛋白表达水平。
结果
EMP3 是多种恶性肿瘤和高级别脑胶质瘤中的 EMT 相关基因。EMP3 在高级别脑胶质瘤和异柠檬酸脱氢酶（IDH）野生型脑胶质瘤中富集。EMP3 可作为诊断脑胶质瘤患者的特异性生物标志物。它也是脑胶质瘤患者总生存期（OS）的独立预后因素。此外，沉默 EMP3 可降低胶质母细胞瘤细胞的增殖和迁移。机制上，EMP3 通过促进 EMT 增强肿瘤细胞的恶性潜能。
结论
EMP3 促进 GBM 细胞的增殖和迁移，其机制可能与 EMP3 促进 GBM 中的 EMT 过程有关；EMP3 可能是 GBM 的独立预后因素。
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