Department of Neurosurgery, The First Hospital of China Medical University, Shenyang, 110001, Liaoning, China.
Department of Neurosurgery, The Second Hospital of Dalian Medical University, Dalian, 116027, Liaoning, China.
J Mol Neurosci. 2020 Oct;70(10):1521-1532. doi: 10.1007/s12031-020-01620-w. Epub 2020 Jul 8.
Serine Incorporator 2 (SERINC2) is a transmembrane protein that incorporates serine into membrane lipids. The function of SERINC2 in tumors has been reported, but the role of SERINC2 in gliomas is not fully understood. RNA-sequencing data from The Cancer Genome Atlas (TCGA) (530 cases of low-grade glioma (LGG) and 173 cases of glioblastoma multiforme (GBM)) and microarray data from Gene Expression Omnibus (GEO) (Accession No. GSE16011, 284 cases gliomas were included) were acquired. Bioinformatics analysis was performed as the primary method to examine the function of SERINC2 and its correlated genes in glioma. SERINC2 was highly expressed in GBM compared with LGG and normal brain tissues. Elevated SERINC2 expression predicted shorter 5-, 10-, and 15-year overall survival (OS) of LGG patients and isocitrate dehydrogenase-1 (IDH-1) mutation-type LGG patients but had no effect on the OS of GBM patients. Cox regression analysis showed that SERINC2 was an independent factor in LGG OS. Methylation analysis found that 13 CpG methylation sites (methylation450k) correlated with SERINC2 expression in LGG. The mRNA expression level of SERINC2 was significant lower in the DNA deletion group than in the intact and amplification groups. A total of 390 copositive and 244 conegative correlation genes with SERINC2 were obtained from LGG in TCGA-LGG and GSE16011. Gene ontology (GO) category and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that the copositive correlation genes were primarily enriched in the mitotic process and cell cycle. Combining the results from the protein-protein interaction (PPI) network of SERINC2 correlation genes and CytoHubba led to the selection of 10 hub genes (CDC20, FN1, AURKB, AURKA, KIF2C, BIRC5, CCNB2, UBE2C, CCNA2, and CENPE). OncoLnc analysis confirmed that high expression levels of these hub genes were associated with poor OS in LGG. Our results suggested that aberrant SERINC2 expression existed in glioma and that its expression might be a potential prognostic marker in LGG patients. CDC20, FN1, AURKB, AURKA, KIF2C, BIRC5, CCNB2, UBE2C, CCNA2, and CENPE may be potential biomarkers and therapeutic targets for LGG.
丝氨酸掺入蛋白 2（SERINC2）是一种跨膜蛋白，可将丝氨酸掺入膜脂质中。已经报道了 SERINC2 在肿瘤中的功能，但 SERINC2 在神经胶质瘤中的作用尚不完全清楚。从癌症基因组图谱（TCGA）（530 例低级别神经胶质瘤（LGG）和 173 例多形性胶质母细胞瘤（GBM））获得 RNA 测序数据和基因表达综合数据库（GEO）（注册号 GSE16011，包括 284 例神经胶质瘤）获得了微阵列数据。作为主要方法，采用生物信息学分析来研究 SERINC2 及其相关基因在神经胶质瘤中的功能。与正常脑组织相比，GBM 中 SERINC2 的表达水平较高。SERINC2 表达升高预示着 LGG 患者和异柠檬酸脱氢酶-1（IDH-1）突变型 LGG 患者的 5 年、10 年和 15 年总生存率（OS）较短，但对 GBM 患者的 OS 没有影响。Cox 回归分析显示，SERINC2 是 LGG OS 的一个独立因素。甲基化分析发现，在 LGG 中，13 个 CpG 甲基化位点（甲基化 450k）与 SERINC2 的表达相关。与完整组和扩增组相比，DNA 缺失组的 SERINC2 mRNA 表达水平显著降低。从 TCGA-LGG 和 GSE16011 中的 LGG 中总共获得了 390 个 copositive 和 244 个 conegative 与 SERINC2 相关的基因。GO 类别和京都基因与基因组百科全书（KEGG）途径分析表明，copositive 相关基因主要富集在有丝分裂过程和细胞周期中。结合 SERINC2 相关基因的蛋白质-蛋白质相互作用（PPI）网络和 CytoHubba 的结果，选择了 10 个枢纽基因（CDC20、FN1、AURKB、AURKA、KIF2C、BIRC5、CCNB2、UBE2C、CCNA2 和 CENPE）。OncoLnc 分析证实，这些枢纽基因的高表达水平与 LGG 患者的不良 OS 相关。我们的结果表明，异常的 SERINC2 表达存在于神经胶质瘤中，其表达可能是 LGG 患者潜在的预后标志物。CDC20、FN1、AURKB、AURKA、KIF2C、BIRC5、CCNB2、UBE2C、CCNA2 和 CENPE 可能是 LGG 的潜在生物标志物和治疗靶点。
