胃癌组织中Cyr61和核因子-κB的表达与转移及预后的关系

Relationship of cysteine-rich protein 61 and NF-κB expression with metastasis and prognosis of gastric carcinoma

目的检测胃癌组织中富含半胱氨酸肝素结合蛋白61（Cyr61）和核因子-κB（NF-κB）的表达及其与临床病理特征及预后的关系。方法应用逆转录聚合酶链反应技术验证和检测53例胃癌组织与11例非肿瘤胃黏膜中Cyr61基因的表达，并用免疫组织化学方法（SP法）检测99例胃癌组织与25例非肿瘤胃黏膜中Cyr61与NF-κB蛋白的表达情况。结果胃癌原发灶和转移灶中Cyr61mRNA的阳性表达率分别为84．6％（22／26）、88．9％（24／27），明显高于非肿瘤胃黏膜组5／11（P值均〈0．05）。非肿瘤胃黏膜、原发癌与转移癌组的基因表达量（2吨^△Ct）分别为（2．76±5．50）×10^-5、（14．61±20．64）×10^-5、（18．46±26．38）×10^-5。胃癌原发灶、转移灶Cyr61 mRNA均高于非肿瘤胃黏膜（P值均〈0．05），转移灶与原发灶比较，差异无统计学意义（P〉0．05）。99例胃癌中Cyr61及NF—κB蛋白的高表达率分别为56．6％（56／99）和55．6％（55／99），其表达水平与肿瘤浸润深度、脉管侵犯、淋巴结转移、远处转移及TNM分期呈正相关（P值均〈0．05），NF—κB还与肿瘤大小呈正相关（P〈0．05）；Cyr61蛋白的表达水平与NF—κB呈正相关（P〈0．05）；Cyr61与NF-κB蛋白高表达的病例平均生存时间和5年生存率明显低于低表达的病例（P值均〈0．05）。结论Cyr61和NF—κB阳性表达与胃癌的侵袭、转移密切相关，检测Cyr61和NF-κB的表达可作为判断胃癌生物学行为的重要参考指标。

Objective To investigate the expression of cysteine-rich protein 61 （ Cyr61 ） and NF- κB in gastric carcinoma and its correlation with the clinicopathologic features and survival time. Methods RT-PCR was used to validate and detect expression of Cyr61 mRNA in 53 gastric carcinoma specimens and 11 non-tumor gastric mucosa samples. Cyr61 and NF-κB protein levels expressed were detected using immunohistochemistry in 99 gastric carcinoma specimens and 25 non-tumor gastric mucosa samples. Results RT-PCR demonstrated that expression of Cyr61 mRNA was higher in the primary carcinoma （84. 6%, 22/26 ） and the metastatic foci （ 88.9% ,24/27 ） than in the non-tumor control samples （ 5/11 ; P 〈 0. 05, respectively）. Cyr61 gene mRNA expression levels were （2. 76 ±5.50） × 10^-5, （14. 61 ±20. 64）× 10^-5, and （18.46 ± 26. 38 ）× 10^-5 by 2-△Ct in the control mucosa samples, primary carcinomas and metastatic tissues respectively. The level was higher in the primary carcinomas and metastatic tissues than that of the non-tumor gastric mucosa （ P 〈 0. 05, respectively） ; however, there was no significant difference between the metastatic tissues and the primary carcinomas （ P 〉 0.05 ）. Immunohistochemistry revealed that of the 99 cases, there was a high expression of Cyr61 and NF-κB protein, 56. 6% （56/99） and 55.6 % （55/99） respectively. There was correlation of Cyr61 and NF-κB protein expressions with the depth of tumor and vascular invasion, as well as the development of lymph node metastasis, and TNM staging （ P 〈 0. 05, respectively）, besides, the expression of NF-κB also correlated with the tumor diameter （P 〈 0. 05 ）. Cyr61 expression was positively correlated with NF-κB expression in gastric carcinoma （ P 〈 0. 05 ） ; the mean survival time in cases with a high expression level of Cyr61 and NF-κB protein was significantly shorter than those with a low expression level （ P 〈 0. 05 ）. Conclusions Expression of Cyr61 and NF-κB closely correlated with invasion and metastasis of gastric carcinoma. They may be considered as the biologic behavior indicators for gastric carcinoma.