胰岛素样生长因子2mRNA结合蛋白表达在胃癌中的预后价值及其对细胞增殖和侵袭的影响

Prognostic value of insulin-like growth factor 2 mRNA-binding protein 2 expression in gastric cancer and its effect on cell proliferation and invasion

目的检测人胰岛素样生长因子2 mRNA结合蛋白2(IGF2BP2)在人胃癌组织的表达及其与患者临床生物学特征和预后的关系,探讨IGF2BP2对胃癌细胞增殖和侵袭的作用.方法肿瘤基因组图谱(TCGA)RNA测序数据库分析IGF2BP2在385例人胃癌组织、32例癌旁组织的表达及其与患者生存和复发的关系.利用小干扰RNA在胃癌MKN-45细胞株敲低IGF2BP2,实时定量反转录聚合酶链反应(RT-qPCR)和蛋白质印迹法(Westem blot)检测IGF2BP2、增殖细胞核抗原(PCNA)和基质金属蛋白酶-2(MMP-2)的表达水平.噻唑蓝(MTT)和Transwell实验检测IGF2BP2沉默对胃癌细胞增殖和侵袭的影响.结果与癌旁组织比较,IGF2BP2在非配对和配对胃癌组织的表达水平均明显升高(t=7.005、7.448,P<0.01),其高表达与患者性别密切相关(x^2=13.975,P<0.01),但与其他临床病理学因素无明显相关(x^2=2.606,P>0.05);Kaplan-Meier分析显示,与IGF2BP2低表达患者比较,高表达患者生存时间减少(x^2=3.821,P<0.05).体外实验显示,IGF2BP2沉默减少PCNA和MMP-2蛋白表达,抑制胃癌细胞增殖活性.与空载组(241.2±19.3)穿过小室的细胞数比较,IGF2BP2沉默组胃癌侵袭细胞数(91.5±8.2)明显减少(t=5.263,P<0.01).结论IGF2BP2高表达与胃癌患者性别和不良生存密切相关,其沉默能抑制胃癌细胞的增殖和侵袭潜能.

Objective To detect the expression levels of insulin-like growth factor 2 mRNA-binding protein 2(IGF2BP2)and its association with the clinicopathological parameters and prognostic value in patients with gastric cancer,and assess its effects on cell proliferation and invasion of gastric cancer cells.Methods The expression levels of IGF2BP2 in 385 cases of gastric cancer samples and 32 corresponding adjacent non-cancer tissues were examined by TCGA RNA-seq data.Gastric cancer MKN-45 cell line stably transfected with siRNA-mediated IGF2BP2 silencing was constructed and the expression levels of IGF2BP2,proliferating cell nuclear antigen(PCNA)and metalloproteinase-2(MMP-2)were detected by real-time quantitative reverse transcriptase-polymerase chain reaction(RT-qPCR)and Western blotting assays.The proliferative activity and metastatic capability of gastric cancer cells were evaluated by methyl thiazol tetrazolium(MTT)and Transwell assays.Results The expression levels of IGF2BP2 were markedly increased in paired and unpaired gastric cancer tissues,as compared with the adjacent non-cancer tissues(t=7.005、7.448,P<0.01).High expression of IGF2BP2 was associated with the gender(χ^2=13.975,P<0.01)but had no obviously association with other clinicopathological factors in patients with gastric cancer(χ^2=2.606,P>0.05).Kaplan-Meier analysis showed that,the patients with high IGF2BP2 expression had a poorer survival as compared with those with low IGF2BP2 expression(χ^2=3.821,P<0.05).Silencing of IGF2BP2 gene downregulated the expression of PCNA and MMP-2.The number of invasive cell of gastric cancer in IGF2BP2 in silencing group(91.5±8.2)was significantly lower than that in the empty group(241.2±19.3)(t=5.263,P<0.01).Conclusion High expression of IGF2BP2 is associated with the gender and poor survival in patients with gastric cancer,and its silencing inhibits the proliferation and invasion of gastric cancer cells.