子宫内膜样腺癌中胰岛素样生长因子及其受体基因表达模式探讨

Expression pattern of insulin-like growth factors and their receptors in endometrioid adenocarcinoma

目的探讨胰岛素样生长因子1(IGF-1)和IGF-2以及它们的受体、结合蛋白IGFBP-3在子宫内膜样腺癌中的表达模式,同时分析它们之间的相互关系。方法选择58例临床不同期别的子宫内膜样腺癌组织标本,同时选取癌旁组织31例、正常内膜组织42例作为对照组,采用Trizol一步法提取总RNA。TaqMan荧光实时定量聚合酶链反应(PCR)检测对照组、内膜癌组、癌旁组的IGF-1、IGF-2、IGF-1R、IGF-2R、IGFBP-3的mRNA表达,分析它们在三组中的表达差异以及相关关系。结果 IGF-1、IGF-1R、IGF-2、IGF-2R、IGFBP-3mRNA表达量在内膜癌组中分别为1.19±0.79、6.23±3.98、2.44±2.32、4.32±2.98、14.47±12.31,在癌旁组中分别为2.66±1.73、35.34±22.02、8.59±7.13、0.39±0.36、8.28±4.57,前两组均明显高于对照组中0.58±0.30、0.54±0.32、0.33±0.19、0.04±0.03、4.85±3.35,差异均有统计学意义;癌旁组与内膜癌组比较,IGF-1、IGF-1R、IGF-2的mRNA量明显升高,IGF-2R、IGFBP-3的mRNA值则下降,差异均有统计学意义。对照组中IGF-1与IGF-1R、IGF-1与IGF-2R、IGF-1与IGFBP-3、IGF-2与IGFBP-3、IGF-1R与IGFBP-3均呈中度正相关,相关系数分别为0.479、0.331、0.305、0.486、0.385,P值均<0.05,其他组合相关性没有统计学意义;内膜癌组中上述组合相关性不明显,只有IGF-1与IGF-2呈高度正相关,相关系数为0.901,P<0.05;癌旁组中,IGF-1与IGF-1R、IGF-2与IGF-1R呈高度正相关,相关系数分别为0.588、0.753,P<0.05,其他组合没有相关性。在内膜癌组中按手术病理分期、细胞分级及肌层浸润深度分组,IGF-1、IGF-2、IGF-2RmRNA表达量随着分期、分级、浸润深度的增加呈下降趋势,差异有统计学意义。结论内膜癌组织和癌旁组织中IGF-1、IGF-2、IGF-1RmRNA呈明显的高表达,以癌旁组织中更明显;IGF-1、IGF-2、IGF-1R基因高活性,可能是正常内膜向癌进展的早期高危信号。IGF-1、IGF-2、IGF-2RmRNA高表达可能提示子宫内膜样腺癌预后良好。

Objective To investigate the IGFs-mRNA expression level in endometrial adenocarcinoma and the relationship between their expression.Methods 58 specimens of endometrial adenocarcinoma and 42 normal endometrial tissue and 31 adjacent cancer lesion(paracancer) tissue were collected in Jingling hospital during Jan 2007 to Jul 2009.The total RNA was extracted using one-step Trizol method.The expressions of IGF-1,IGF-1R,IGF-2,IGF-2R,IGFBP-3 mRNA in the control group(normal endometrial tissue),endometrial carcinoma and paracancer group were detected by TaqMan fluorescent real-time quantitative PCR.The differentiation of their expression in three groups and the correlation between their expression pattern in endometrial carcinoma were analysed.Results The expression level of IGF-1,IGF-1R,IGF-2,IGF-2R,IGFBP-3 mRNA were 1.19±0.79,6.23±3.98,2.44±2.32,4.32±2.98,14.47±12.31 in cancer group,2.66±1.73,35.34±22.02,8.59±7.13,0.39±0.36,8.28±4.57 in paracancer group,and 0.58±0.30,0.54±0.32,0.33±0.19,0.04±0.03,4.85±3.35 in normal endometrium.The expression levels in endometrial cancer tissues and paracancer tissues were significantly higher than that in control group(P<0.05),while the level of IGF-1,IGF-1R,IGF-2 mRNA increased and IGF-2R,IGFBP-3 mRNA decreased in paracancer group(P<0.05) compared with endometrial cancer group.In control group,the moderately positive correlations between IGF-1 and IGF-1R,IGF-1 and IGF-2R,IGF-1 and IGFBP-3,IGF-2 and IGFBP-3,IGF-1R and IGFBP-3 were observed(rs=0.479,0.331,0.305,0.486,0.385,respectively,P<0.05).There was no statistically significant correlation between other associated pairs.Only IGF-1 was strongly positively correlated with IGF-2 in endometrial cancer group(rs=0.901,P<0.05),the correlations that showed in control were not present.The highly positive correlation between IGF-1 and IGF-1R,IGF-2 and IGF-1R were observed in paracancer tissue(rs=0.588,0.753,P <0.05).The expression of IGF-1,IGF-2,IGF-2R mRNA in endometrioid adenocarcinoma decreased with the stage,grade and depth of infiltration increased.Conclusions The activity of IGF-1,IGF-2,IGF-1R genes in paracancer tissue and in endometrial cancer tissue was markedly increased.It was a potential early high-risk signal in progression of endometrial carcinoma.The overexpression of IGF-1,IGF-2,IGF-1R mRNA might predict a good prognosis of patient with endometrioid adenocarcinoma.