摘要
背景:目前临床上尚无有效预测胃癌前病变进展或筛查早期胃癌的生物学标志物.目的:研究腺苷酸环化酶7(ADCY7)、G蛋白偶联受体GPR86、N-甲基-D-天冬氨酸离子能谷氨酸受体2D(GRIN2D)、G蛋白信号调节因子4(RGS4)在不同胃黏膜病变中的表达及其对胃癌前病变进展的预测价值.方法:应用免疫组化法、real-time PCR和蛋白质印迹法检测ADCY7、GPR86、GRIN2D、RGS4在Correa级联各阶段(包括慢性非萎缩性胃炎、慢性萎缩性胃炎、低级别和高级别上皮内瘤变、黏膜层和黏膜下层早期胃癌)以及胃癌与相应癌旁组织间的表达差异.结果:ADCY7、GPR86、GRIN2D、RGS4在胃炎、上皮内瘤变、早期胃癌中的表达呈递增趋势,除GRIN2D在上皮内瘤变与早期胃癌中的表达无明显差异外,两两比较差异均有统计学意义(P均<0.001).GPR86、GRIN2D mRNA和蛋白在胃癌组织中的表达显著高于癌旁>5 cm组织(P均<0.05);RGS4蛋白在胃癌组织中的表达高于癌旁>5 cm组织,其mRNA表达趋势则相反(P均<0.05);ADCY7仅蛋白表达在胃癌与癌旁>5 cm组织间差异显著(P<0.05).结论:ADCY7、GPR86、GRIN2D、RGS4在Correa级联各阶段以及胃癌与相应癌旁组织间的表达变化提示其参与了胃癌前病变的发生、发展,可能具有预测胃癌前病变进展的价值.
Abstract
Background:Currently,there are no effective biomarkers for predicting the progression of gastric precancerous lesions or screening early gastric cancer in clinical practice.Aims:To explore the expressions of adenylate cyclase 7(ADCY7),G protein-coupled receptor GPR86,glutamate receptor,ionotropic,N-methyl D-aspartate 2D(GRIN2D)and regulator of G protein signaling 4(RGS4)in various gastric mucosal lesions and their predictive value for progression of gastric precancerous lesions.Methods:Expressions of ADCY7,GPR86,GRIN2D,and RGS4 were detected by immuno-histochemistry,real-time PCR and Western blotting in Correa cascade(chronic non-atrophic gastritis,chronic atrophic gastritis,low-and high-grade intraepithelial neoplasia,and mucosal and submucosal early gastric cancer)and cancerous and para-cancerous tissues,among which,the differences in expression levels of these four factors were analyzed.Results:There was an increasing tendency in expression levels of ADCY7,GPR86,GRIN2D,and RGS4 from gastritis,intra-epithelial neoplasia to early gastric cancer.Except for GRIN2D expression between intraepithelial neoplasia and early gastric cancer,significant differences could be observed in any two groups(all P<0.001).Both mRNA and protein expression levels of GRP86 and GRIN2D were significantly higher in cancerous tissue than in adjacent tissue>5 cm(all P<0.05).Protein expression of RGS4 was significantly higher in cancerous tissue than in adjacent tissue>5 cm,but its mRNA expression presented an opposite trend(all P<0.05).Significant difference between cancerous tissue and adjacent tissue>5 cm in ADCY7 expression was only existed at protein level(P<0.05).Conclusions:Alterations of the expression levels of ADCY7,GPR86,GRIN2D,and RGS4 in Correa cascade and cancerous and para-cancerous tissues suggest that they are involved in the occurrence and development of gastric precancerous lesions,and might be used as predictors for progression of gastric precancerous lesions.
NETL
NSTL
万方数据