Epidermal growth factor receptor (EGFR) and lanthionine synthetase C-like 2 (LanCL2) genes locate in the same amplicon, and co-amplification of EGFR and LANCL2 is frequent in glioblastoma. However, the prognostic value of LANCL2 and EGFR co-amplification, and their mRNA and protein expression in glioblastoma remain unclear yet. This study analyzed the prognostic values of the copy number variations (CNVs), mRNA and protein expression of LANCL2 and EGFR in 575 glioblastoma patients in TCGA database and 100 glioblastoma patients in tumor banks of the Shenzhen Second People’s Hospital and the Sun Yat-sen University Cancer Center. The amplification of LANCL2 or EGFR, and their co-amplification were frequent in glioblastoma of TCGA database and our tumor banks. A significant correlation was found between the CNVs of LANCL2 and EGFR (p < 0.001). CNVs of LANCL2 or EGFR were significantly correlated with IDH1/2 mutation but not MGMT promoter methylation. Multivariate analysis showed that LANCL2 amplification was significantly correlated with reduced overall survival (OS) in younger (< 60 years) glioblastoma patients of TCGA database (p = 0.043, HR = 1.657) and our tumor banks (p = 0.018, HR = 2.199). However, LANCL2 or EGFR amplification, and their co-amplification had no significant impact on OS in older (≥ 60 years) or IDH1/2-wild-type glioblastoma patients. mRNA and protein overexpression of LANCL2 and EGFR was also frequently found in glioblastoma. The mRNA expression rather than the protein expression of LANCL2 and EGFR was positively correlated (p < 0.001). However, mRNA or protein expression of EGFR and LANCL2 was not significantly correlated with OS of glioblastoma patients. The protein expression level of LANCL2, rather than EGFR, was elevated in relapsing glioblastoma, compared with newly diagnosed glioblastoma. In addition, the intracellular localization of LanCL2, not EGFR, was associated with the grade of gliomas. Taken together, amplification and mRNA overexpression of LANCL2 and EGFR, and their co-amplification and co-expression were frequent in glioblastoma patients. Our findings suggest that amplification of LANCL2 and EGFR were the independent diagnostic biomarkers for glioblastoma patients, and LANCL2 amplification was a significant prognostic factor for OS in younger glioblastoma patients.

中文翻译：

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在胶质母细胞瘤患者中鉴定由拷贝数变异、LANCL2 和 EGFR 的 mRNA 和蛋白质表达定义的预后值

表皮生长因子受体（EGFR）和羊毛硫氨酸合成酶C样2（LanCL2）基因位于同一扩增子中，EGFR和LANCL2共同扩增在胶质母细胞瘤中很常见。然而，LANCL2 和 EGFR 共扩增的预后价值，以及它们在胶质母细胞瘤中的 mRNA 和蛋白表达仍不清楚。本研究分析了 TCGA 数据库中 575 例胶质母细胞瘤患者和深圳市第二人民医院和中山大学肿瘤库中 100 例胶质母细胞瘤患者中 LANCL2 和 EGFR 的拷贝数变异（CNVs）、mRNA 和蛋白表达的预后价值。癌症中心。LANCL2或EGFR的扩增及其共同扩增在TCGA数据库和我们的肿瘤库的胶质母细胞瘤中很常见。LANCL2 和 EGFR 的 CNV 之间存在显着相关性（p < 0.001）。LANCL2 或 EGFR 的 CNV 与 IDH1/2 突变显着相关，但与 MGMT 启动子甲基化无关。多变量分析显示 LANCL2 扩增与 TCGA 数据库 (p = 0.043, HR = 1.657) 和我们的肿瘤库 (p = 0.018, HR = 2.199) 的年轻 (< 60 岁) 胶质母细胞瘤患者的总生存期 (OS) 降低显着相关. 然而，LANCL2 或 EGFR 扩增及其共同扩增对老年（≥ 60 岁）或 IDH1/2 野生型胶质母细胞瘤患者的 OS 没有显着影响。在胶质母细胞瘤中也经常发现 LANCL2 和 EGFR 的 mRNA 和蛋白质过表达。LANCL2和EGFR的mRNA表达而非蛋白表达呈正相关（p <0.001）。然而，EGFR 和 LANCL2 的 mRNA 或蛋白表达与胶质母细胞瘤患者的 OS 无显着相关性。与新诊断的胶质母细胞瘤相比，复发性胶质母细胞瘤中 LANCL2 而非 EGFR 的蛋白表达水平升高。此外，LanCL2 而非 EGFR 的细胞内定位与胶质瘤的分级有关。总之，LANCL2 和 EGFR 的扩增和 mRNA 过表达，以及它们的共扩增和共表达在胶质母细胞瘤患者中很常见。我们的研究结果表明，LANCL2 和 EGFR 的扩增是胶质母细胞瘤患者的独立诊断生物标志物，LANCL2 扩增是年轻胶质母细胞瘤患者 OS 的重要预后因素。与胶质瘤的分级有关。总之，LANCL2 和 EGFR 的扩增和 mRNA 过表达，以及它们的共扩增和共表达在胶质母细胞瘤患者中很常见。我们的研究结果表明，LANCL2 和 EGFR 的扩增是胶质母细胞瘤患者的独立诊断生物标志物，LANCL2 扩增是年轻胶质母细胞瘤患者 OS 的重要预后因素。与胶质瘤的分级有关。总之，LANCL2 和 EGFR 的扩增和 mRNA 过表达，以及它们的共扩增和共表达在胶质母细胞瘤患者中很常见。我们的研究结果表明，LANCL2 和 EGFR 的扩增是胶质母细胞瘤患者的独立诊断生物标志物，LANCL2 扩增是年轻胶质母细胞瘤患者 OS 的重要预后因素。