Abstract
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.
Highlights
Glioma is the most common primary malignant brain tumor, and it is derived from glial cells with a high infiltrativeJ Mol Neurosci (2020) 70:1521–1532Serine Incorporator 2 (SERINC2) is a transmembrane protein that belongs to the SERINC family, and it functions to transform serine into lipid membranes during synthesis (Inuzuka et al 2005)
Data mining from The Cancer Genome Atlas (TCGA) showed that SERINC2 expression in 530 cases of low-grade glioma (LGG) was lower than that in 173 cases of glioblastoma multiforme (GBM)
SERINC2 expression in GSE16011 showed that compared with LGG and normal brain tissues, higher expression of SERINC2 occurred in GBM (Fig. 1a–b)
Summary
Glioma is the most common primary malignant brain tumor, and it is derived from glial cells with a high infiltrativeJ Mol Neurosci (2020) 70:1521–1532SERINC2 is a transmembrane protein that belongs to the SERINC family, and it functions to transform serine into lipid membranes during synthesis (Inuzuka et al 2005). SERINC plays essential roles in regulating the biosynthesis of multiple membrane lipids, such as phosphatidylserine and sphingolipid molecules (Ren et al 2014). Phosphatidylserine and sphingolipids play critical roles in tumorigenesis and cancer progression (Chang et al 2000; He et al 2009; Lee et al 2012). Phosphatidylserine is induced by scramblase to be exposed on the surface of glioma cells from the normal expression type of an intramembrane model, and this process promotes the phagocytosis of microglial cells (Lee et al 2012). Interference with distinct steps of sphingolipid synthesis and signaling attenuates the proliferation of glioma cells (Bernhart et al 2015). We created a PPI network using correlation genes with SERINC2 to investigate the underlying mechanisms involved in glioma tumorigenesis
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