二脂酰甘油酰基转移酶2在神经母细胞瘤中的表达及与MYCN表达相关性的分析OA

[Objective]To explore the key genes influencing diacylglycerol metabolism in neuroblastoma(NB),clarify the expression and clinical significance of diacylglycerol acyltransferase 2(DGAT2)in NB,and provide a theoretical basis for the diagnosis and targeted therapy of NB.[Methods]NB transcriptome data were obtained from GEO(GSE49710)and TCGA(TARGET-NBL)databases.Differentially expressed genes(DEGs)commonly upregulated in MYCN-amplified groups were screened,and the key gene DGAT2 was identified by intersecting the screened DEGs with the diacylglycerol metabolism-related gene set followed by prognostic analysis and comparison.The expression of DGAT2 was analyzed via the R2 database.The potential impact of DGAT2 on the immune microenvironment was explored by combining the single-cell dataset GSE137804.Immunohistochemistry(IHC)was used to detect the expression level of DGAT2 and its correlation with MYCN expression in 55 clinical NB tissues and mouse xenograft tumor tissues.[Results]A total of 907 DEGs commonly upregulated in the MYCN-amplified groups were screened,among which three DEGs were highly expressed in the diacylglycerol metabolism-related gene set(P＜0.05).After comparison,DGAT2 was found to have the most significant impact on prognosis(HR=1.4,95%CI:1.2,1.7;P=5.41×10-7).Survival analysis showed that patients with high DGAT2 expression had a significantly shorter overall survival.Single-cell analysis revealed that high expression of DGAT2 led to an immunosuppressive microenvironment in NB.IHC results showed that the expression of DGAT2 in NB tissues was significantly positively correlated with MYCN expression in the tumor tissue microarrays of clinical NB patients and the tissues of mouse ectopic xenograft tumors(rs=0.369 4,P＜0.01).[Conclusions]DGAT2 is highly expressed in MYCN-amplified NB,and may independently predict poor prognosis in NB patients.It is expected to become a diagnostic marker for NB and a potential therapeutic target for MYCN-amplified NB.