谷氨酰胺酶1在胃癌中的作用和机制探讨

The exploration on the role and mechanism of GLS1 in gastric cancer

目的谷氨酰胺酶1(GLS1)在胃癌中高表达,通过生物信息学探索GLS1在胃癌中的作用和机制。方法应用多个数据库(包括TIMER,UALCAN和MethPrimer)分析GLS1在胃癌中高表达的原因、GLS1的表达与免疫细胞浸润之间的相关性,实验验证靶向GLS1对于胃癌肿瘤细胞增殖能力的影响。结果生物信息学分析发现:GLS1的高表达与基因突变没有明显的相关性,而与TP53基因突变和启动子区域甲基化有明显的相关性;胃癌中GLS1的表达与多种免疫细胞的浸润明显相关,并且与PD-L1(CD274)和CTLA4的表达呈正相关关系,在一定程度上可以预测PD-L1治疗的疗效;用特异性的siRNA敲低GLS1的表达,可以抑制胃癌肿瘤细胞的增殖,新型GLS1的抑制剂Compound 968可以更好地抑制胃癌肿瘤细胞的增殖。结论GLS1在胃癌中高表达主要是与TP53基因突变和启动子区域甲基化明显相关,胃癌中GLS1的表达与免疫因素密切相关,靶向GLS1可以抑制胃癌肿瘤细胞的增殖能力。

Objective Glutaminase 1(GLS1)is highly expressed in gastric cancer.This study explored the role and mechanism of GLS1 in gastric cancer by bioinformatics.Methods The reasons for GLS1 high expression in gastric cancer and the correlation between GLS1 expression and immune cell infiltration were analyzed via multiple databases(TIMER,UALCAN and MethPrimer),and the effect of targeting GLS1 on the proliferation of gastric cancer cells was verified through experiments.Results Bioinformatics analysis showed that the high expression of GLS1 was not correlated with gene mutation,but was correlated with TP53 gene mutation and promoter methylation.The expression of GLS1 in gastric cancer was significantly correlated with the infiltration of a variety of immune cells,and was positively correlated with the expression of PD-L1(CD274)and CTLA4,which could predict the efficacy of PD-L1 treatment to a certain degree.Knocking down the expression of GLS1 with specific siRNA could inhibit the proliferation of gastric cancer cells.Compound 968,a new GLS1 inhibitor,could more effectively inhibit the proliferation of gastric cancer cells.Conclusion The high expression of GLS1 in gastric cancer is mainly related with TP53 gene mutation and promoter methylation.The expression of GLS1 in gastric cancer is strongly related with immune factors.Targeting GLS1 could inhibit the proliferation of gastric cancer cells.