ADAMTS9-AS1-SEMA3G通路对胰腺癌组织中免疫细胞的影响

ADAMTS9-AS1-SEMA3G affects the infiltration of immune cells in pancreatic cancer

目的影响胰腺癌中免疫细胞浸润的机制尚未明确。文章旨在研究胰腺癌中影响免疫浸润相关的lncRNA-mRNA调控通路。方法利用TCGA以及GEO基因表达数据筛选共同的差异lncRNAs,并对筛选出的差异lncRNAs进行生存分析、靶基因预测、GO、KEGG富集分析、免疫浸润分析以及基因集富集分析(GSEA),找到免疫浸润相关通路。结果 ADAMTS9-AS1高表达的胰腺癌患者较低表达患者有更高的生存率(P=0.010)。ADAMTS9-AS1相关性较强的差异mRNA,GO富集结果共筛选到356个条目,结果与免疫相关,如白细胞-细胞黏附、肿瘤坏死因子超家族细胞因子产生的调控等;KEGG结果共筛选到9个通路,分别为金黄色葡萄球菌感染、细胞周期、补体和凝血级联、卵母细胞减数分裂、孕酮介导的卵母细胞成熟、破骨细胞分化、类风湿关节炎、百日咳以及人T细胞白血病病毒1感染。对照IMMPORT数据库中2498个肿瘤免疫相关基因,发现SEMA3G为免疫相关基因,且与ADAMTS9-AS1相关性最高(r=0.657,P<0.05)。ADAMTS9-AS1及SEMA3G的表达与免疫细胞浸润呈正相关(P<0.05)。GSEA富集分析结果显示ADAMTS9-AS1也可能与柠檬酸盐循环、脂肪酸代谢、甘氨酸、丝氨酸和苏氨酸代谢、溶酶体、过氧化物酶体、丙酸盐代谢、蛋白酶体、丙酮酸盐代谢、核糖体、缬氨酸-亮氨酸和异亮氨酸降解通路相关。结论 ADAMTS9-AS1-SEMA3G与胰腺癌的预后和免疫浸润水平相关,可为后续的基因验证实验和免疫研究提供理论依据。

Objective The mechanism that affects the infiltration of immune cells in pancreatic cancer has not yet been clarified. This study aims to investigate the lncRNA mRNA regulatory pathways that affect immune infiltration in pancreatic cancer. Methods TCGA and GEO gene expression data were used to screen common differential lncRNAs. We perform survival analysis, target gene prediction, GO, KEGG enrichment analysis, immune infiltration analysis, gene set enrichment analysis(GSEA) on the selected differential lncRNAs to identify the relevant pathways of immune infiltration. Results The pancreatic cancer patients with high expression of ADAMTS9 AS1 have a higher survival rate when compared to patients with low expression(P=0.010). The combined analysis of TCGA and GSE86436 revealed the difference and survival-related ADAMTS9 AS1. The functional prediction of ADAMTS9 AS1 was related to immunity. Using the TIMER database, the lncRNA affected the infiltration of immune cells in pancreatic cancer tissues. The clinical analysis was demonstrated that the ADAMTS9 AS1 was related to pathological grade. The target gene SEMA3 G was screened by co-expression analysis using the IMMPORT database and TIMER database. Lastly, GSEA analysis of ADAMTS9-AS1 showed that the lncRNA was also related to tumor metabolism. ConclusionThese results indicate that ADAMTS9-AS1-SEMA3 G is associated with the prognosis and immune invasion level of pancreatic cancer, which can provide a theoretical basis for subsequent genetic verification experiments and immune research.