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Serine Incorporator 2 (SERINC2) Expression Predicts an Unfavorable Prognosis of Low-Grade Glioma (LGG): Evidence from Bioinformatics Analysis.
Journal of Molecular Neuroscience ( IF 2.8 ) Pub Date : 2020-07-08 , DOI: 10.1007/s12031-020-01620-w
Chunxiao Qi 1, 2 , Lei Lei 3 , Jinqu Hu 1 , Gang Wang 1 , Jiyuan Liu 1 , Shaowu Ou 1
Affiliation  

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.



中文翻译:

Serine Incorporator 2 (SERINC2) 表达预测低级胶质瘤 (LGG) 的不利预后:来自生物信息学分析的证据。

Serine Incorporator 2 (SERINC2) 是一种跨膜蛋白,可将丝氨酸结合到膜脂中。SERINC2在肿瘤中的功能已有报道,但SERINC2在胶质瘤中的作用尚不完全清楚。来自癌症基因组图谱 (TCGA) 的 RNA 测序数据(530 例低级别胶质瘤 (LGG) 和 173 例多形性胶质母细胞瘤 (GBM))和来自基因表达综合 (GEO) 的微阵列数据(登录号 GSE16011, 284病例包括胶质瘤)获得。进行生物信息学分析作为检查 SERINC2 及其相关基因在胶质瘤中的功能的主要方法。与 LGG 和正常脑组织相比,SERINC2 在 GBM 中高表达。升高的 SERINC2 表达预测更短的 5-、10-、LGG 患者和异柠檬酸脱氢酶-1 (IDH-1) 突变型 LGG 患者的 15 年总生存期 (OS) 但对 GBM 患者的 OS 没有影响。Cox回归分析显示SERINC2是LGG OS的独立因素。甲基化分析发现 13 个 CpG 甲基化位点 (methylation450k) 与 LGG 中的 SERINC2 表达相关。DNA缺失组SERINC2的mRNA表达水平显着低于完整组和扩增组。从 TCGA-LGG 和 GSE16011 中的 LGG 中总共获得了 390 个与 SERINC2 的共阳性和 244 个共负相关基因。基因本体(GO)类别和京都基因和基因组百科全书(KEGG)通路分析表明,共正相关基因主要在有丝分裂过程和细胞周期中富集。结合 SERINC2 相关基因和 CytoHubba 的蛋白质-蛋白质相互作用 (PPI) 网络的结果,选择了 10 个中枢基因(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 中较差的 OS 相关。我们的结果表明,神经胶质瘤中存在异常的 SERINC2 表达,其表达可能是 LGG 患者的潜在预后标志物。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。OncoLnc 分析证实,这些枢纽基因的高表达水平与 LGG 中较差的 OS 相关。我们的结果表明,神经胶质瘤中存在异常的 SERINC2 表达,其表达可能是 LGG 患者的潜在预后标志物。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。OncoLnc 分析证实,这些枢纽基因的高表达水平与 LGG 中较差的 OS 相关。我们的结果表明,神经胶质瘤中存在异常的 SERINC2 表达,其表达可能是 LGG 患者的潜在预后标志物。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。

更新日期:2020-07-08
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