AFAP1L1在胃癌中的表达及对胃癌细胞增殖能力的影响

Expression of AFAP1L1 in gastric cancer and its effect on proliferation of gastric cancer cells

目的观察AFAP1L1基因在胃癌中的表达及与患者预后的相关性,并探讨其在胃癌发生、发展中的相关功能及可能机制。方法利用癌症基因组图谱(TCGA)数据分析AFAP1L1在泛癌中的表达差异情况,并通过Kaplan-Meier分析AFAP1L1与胃癌及其他肿瘤预后的相关性。在胃癌中选择与AFAP1L1正相关的前300个基因进行基因本体(GO)富集、京都基因与基因组百科全书(KEGG)信号通路分析。最后利用RNA干扰技术沉默胃癌细胞中AFAP1L1表达后进行细胞计数试剂盒(CCK-8)测定,集落形成测定和裸鼠皮下移植瘤实验评估AFAP1L1对胃癌细胞增殖的影响。多组间比较应用单因素方差分析,两组间比较采用t检验。结果TCGA数据分析显示,AFAP1L1在包括胃癌在内的多种肿瘤中高表达。生存分析结果显示AFAP1L1高表达与胃癌的预后差相关(P<0.05)。基因富集与功能分析显示ALKBH1高表达与细胞增殖相关基因密切相关,沉默AFAP1L1能抑制胃癌细胞的增殖和克隆形成能力,差异有统计学意义(F=23.412、29.153,P<0.05),同时沉默AFAP1L1后裸鼠移植瘤的体积和重量也明显小于对照组,差异有统计学意义(t=12.462、9.541,P<0.05)。结论AFAP1L1在胃癌组织中高表达可作为患者预后不良的分子标志物,可通过促进细胞增殖促进胃癌发生和发展。

Objective To clarify the expression of AFAP1L1 gene in gastric cancer and its correlation with the prognosis of patients,and to explore the related functions and possible mechanisms of AFAP1L1 in the occurrence and development of gastric cancer.Methods The Cancer Genome Atlas(TCGA)data were used to analyze the expression differences of AFAP1L1 in pan-cancers,and the correlation between AFAP1L1 and the clinical prognosis of various tumors was analyzed by Kaplan-Meier.The first 300 genes positively related to AFAP1L1 were selected for gene ontology(GO)enrichment and kyoto encyclopedia of genes and genomes(KEGG)signaling pathway analysis.Finally,cell counting kit-8(CCK-8)assay,colony formation assay and nude mouse subcutaneous xenograft experiment were performed to evaluate the effect of AFAP1L1 on the proliferation of gastric cancer cell lines.One-way ANOVA was used for comparison between multiple groups,and t test was used for comparison between two groups.Results Analysis of TCGA data showed that AFAP1L1 was highly expressed in a variety of tumors including gastric cancer.The results of survival analysis showed that the high expression of AFAP1L1 was correlated with the poor prognosis of gastric cancer(P<0.05).Gene enrichment and functional analysis showed that the high expression of ALKBH1 was related to those genes that are related to cell proliferation and migration.Silencing AFAP1L1 could inhibit the proliferation and colony formation ability of gastric cancer cells,and the difference was statistically significant(F=23.412,29.153,P<0.05).At the same time,the volume and weight of xenografted tumors in nude mice after silencing AFAP1L1 were also significantly smaller than those in the control group(t=12.462,9.541,P<0.05).Conclusion The high expression of AFAP1L1 in gastric cancer tissues can be used as a molecular marker for patients with poor prognosis.AFAP1L1 can promote the occurrence and development of gastric cancer by promoting cell proliferation and immune cell infiltration.