长链非编码RNA PCA3在胃癌中的预后价值及对胃癌细胞株AGS细胞生物学特性的影响

Prognostic value of long-chain non-coding RNA PCA3 in gastric cancer and its effect on biological characteristics of AGS cells

目的通过生物信息学及细胞学实验方法,研究长链非编码RNA(LncRNA)PCA3在胃癌发生发展及预后方面的价值。方法利用癌症基因组图谱(TCGA)和基因型-组织表达数据库(GTEx)中的高通量测序数据,对PCA3的表达及其与临床资料的相关性进行分析。采用肿瘤免疫评估资源(TIMER)数据库分析PCA3在免疫浸润物中的表达及对胃癌患者生存预后的影响。随后通过慢病毒介导的RNA干扰来沉默AGS细胞株中的PCA3表达,并用CCK-8法及Transwell小室法来检测细胞的增殖、迁移及侵袭能力。结果TCGA及GETx数据库分析发现,PCA3在胃癌组织中的表达水平高于正常胃黏膜组织(P<0.0001),且表达越高,患者的总体生存期越短(P<0.01)。相关性分析显示,PCA3的表达与肿瘤T分期及分化程度之间有关联(P<0.05)。TIMER数据库分析显示在免疫微环境中高表达PCA3 mRNA的巨噬细胞对胃癌患者生存预后较差(P<0.05)。与空白对照组及阴性对照组相比,PCA3的表达降低后,胃癌AGS细胞的增殖、迁移及侵袭能力受到抑制(P<0.05)。结论PCA3可能成为一种新型肿瘤标志物,有助于胃癌的早期诊断及预后评估,对促进胃癌诊治及提高患者预后具有一定的价值。

Objective To explore the effects of long-chain non-coding RNA(LncRNA)PCA3 on gastric cancer formation and prognosis by bioinformatics methods and cytological experiments.Methods High-throughput sequencing materials from The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)were used to analyze the PCA3 expression and its correlation with clinical features.The tumor immune estimation resource(TIMER)database was used to analyze the expression of PCA3 in immune infiltrate and its impact on the survival and prognosis of patients with gastric cancer.Subsequently,RNA mediated by lentiviral was applied for the silence of PCA3 expression in AGS cell line.While CCK-8 assay and Transwell chamber assay were implemented to detect cell proliferation,migration and invasion.Results The expression level of PCA3 in gastric cancer tissue was significantly higher than that in gastric mucosal tissue showed by the databases of TCGA and GETX(P<0.0001).The higher PCA3 expressed,the shorter of overall survival time patients had(P<0.01).Correlation analysis showed that the expression of PCA3 was significantly correlated with T stage and tumor differentiation(P<0.05).TIMER database analysis showed that patients with gastric cancer who had macrophages with high expression of PCA3 mRNA in the immune microenvironment had poor survival prognosis(P<0.05).Compared with negative control group and blank control group,the proliferation,migration and invasion ability of gastric cancer AGS cells were significantly inhibited after the expression of PCA3 being reduced(P<0.05).Conclusions PCA3 may become a new tumor marker,which is helpful for the early diagnosis and prognostic evaluation of gastric cancer.It has certain value in promoting the diagnosis and treatment of gastric cancer and improving the prognosis of patients.