GRIM-19在人膀胱尿路上皮癌中的表达及其与p 63、STAT3的相关性研究

摘要

目的：研究 GRIM-19在人膀胱尿路上皮癌(BTCC)组织中的表达和临床意义，以及与 p63、STAT3表达的相关性，探讨 GRIM-19对 p63、STAT3的影响及其在 BTCC 中的作用及机制。方法采用逆转录聚合酶链反应检测76例 BTCC 组织、45例相应的癌旁组织和30例正常膀胱组织的 GRIM-19 mRNA表达，免疫印迹法检测 p63、STAT3蛋白的表达。结果 GRIM-19 mRNA在76例BTCC组织中的阳性表达率为40.79%，显著低于癌旁组织和正常膀胱组织(分别为66.67%和96.67%)(P均<0.05)；p63、STAT3蛋白在BTCC组织中的表达(分别为82.89%、72.37%)显著高于癌旁组织和正常膀胱组织(P均<0.01)。BTCC组织中GRIM-19 mRNA的低表达与肿瘤的病理分级、淋巴转移密切相关，而与患者性别、年龄、临床分期、肿瘤直径和肿瘤发生情况等无相关性。相关性检验表明 GRIM-19 mRNA与 p63、STAT3表达呈显著负相关(P<0.01)。结论 GRIM-19 mRNA在BTCC组织中的表达下调，提示 GRIM-19作为重要的抑癌基因，可能与凋亡相关基因p63、STAT3在BTCC的发展中起拮抗作用，参与 BTCC 的发生和发展过程，并可能是 BTCC 转移的潜在标志。%Objective To investigate the expression and clinical significance of GRIM-19 and its correlation with p63 and STAT3 in the tissues of human bladder transitional cell carcinoma (BTCC),and to investigate the role of GRIM-19 in the BTCC. Methods Reverse transcription polymerase chain reac-tions and Western blotting techniques were respectively used to detect the expressions of GRIM-1 9 mRNA and the proteins of p63 and STAT3 in 76 cases tissues of BTCC,compared with 45 cases of adjacent noncancerous tissues and 30 cases of normal bladder tissues. Results The expression rate of GRIM-19 mRNA in BTCC tissues was 40.79% ,which was significantly lower than those of adja-cent noncancerous tissues (66.67%)and normal tissues (96.67%)(P<0.05).The expression of GRIM-1 9 had significant negative correlation with the degree of differentiation and metastasis of tumor (χ2=16.8 and 8.52,respectively,P<0.01).However,no correlation was found between the expression level and patient age,sexuality,clinical staging and size of tumor tissues (P>0.05). Expressions of the proteins of p63 and STAT3 were negatively correlated with expression of GRIM-19 (χ2=-17.16 and -9.12,respectively,P<0.01). Conclusions Low expression of GRIM-19 in BTCC might induce the expression of p63 and STAT3 in BTCC.As a tumor suppressor,GRIM-19 might play an important role in the process of tumorigenesis and malignant progression of BTCC and could be used as a biomarker of malignance.The apoptosis related genes p63 and STAT3 may respectively have antagonistic roles with GRIM-1 9 gene in the formation and progression of BTCC.