人类主要组织相容性复合物Ⅰ类相关链A在肾肿瘤中的表达及临床意义

Expression and clinical value of major histocompatibility complex class-Ⅰ related chain A molecule in serum of patients with renal tumor

目的 探讨肾肿瘤患者人类主要组织相容性复合物Ⅰ类相关链A（major histocompatibility complex class-Ⅰ related chain A,MICA）的表达及临床意义. 方法 选取2013年3-7月收治的60例肾肿瘤患者作为研究组,男37例,女23例.年龄34 ～ 76岁,平均46岁.肾透明细胞癌48例,肾血管平滑肌脂肪瘤12例.病理分期：T1期20例,T2期14例,T3期10例,T4期4例.淋巴结转移11例,其他器官转移4例.20例健康体检者为对照组,男10例,女10例.年龄24～50岁,平均31岁.利用ELISA法测定两组血清中分泌型MICA（soluble MICA,sMICA）分子的水平.分析sMICA分子含量与肾肿瘤的性质、肾癌分期、淋巴结及器官转移的关系.免疫组化染色法测定15例肾癌及癌旁组织标本的MICA分子表达情况.实时定量PCR法测定9例肾癌和3例癌旁组织标本的MICA-mRNA表达情况. 结果 48例肾癌、12例肾血管平滑肌脂肪瘤、20例对照组的血清sMICA水平分别为（348.5±32.5）、（289.3±30.4）、（168.4±43.2） pg/ml,研究组与对照组比较差异有统计学意义（P＜0.05）,肾癌组与肾血管平滑肌脂肪瘤组比较差异有统计学意义（P＜0.05）.肾肿瘤T1、T2、T3、T4期的sMICA水平分别为（304.3±27.4）、（308.4±26.8）、（368.3±33.4）、（378.4±43.4） pg/ml,T1、T2期间比较差异无统计学意义（P＞0.05）,其余各分期间比较差异有统计学意义（P＜0.05）.伴有淋巴结转移组与无淋巴结转移组的sMICA水平分别为（326.2±32.4）、（319.4±32.5） pg/ml,差异无统计学意义（P＞0.05）.伴有其他器官转移组与无其他器官转移组的sMICA水平分别为（373.4±45.4）、（346.4±31.5） pg/ml,差异有统计学意义（P＜0.05）.免疫组化染色法证实MICA分子在癌组织的细胞表面高表达,而在癌旁细胞表面不表达.实时定量PCR法检测MICA-mRNA在癌组织的表达量（2.03）明显高于癌旁组织（0.77）,差异有统计学意义（P＜0.05）. 结论 MICA在肾肿瘤中高度表达,其表达高低与肾肿瘤的性质、肾癌分期及转移有关.

Objective To explore the expression and clinical value of major histocompatibility complex class-Ⅰ related chain A （sMICA） molecule in serum of patients with renal tumor.Methods From March 2013 to July 2013,60 patients with renal tumor,including 37 male patients and 23 female patients were enrolled in this study as experimental group.The mean age was 46 years （range 34-76 years）.The pathological diagnosis included renal cell carcinoma in 48 cases and renal angiomyolipoma in 12 cases.The stage classification included T1 stage in 20 cases,T2 stage in 14 cases,T3 stage in 10 cases and T4 stage in 4 cases.Lymphatic metastases were found in 11 cases and metastases in other organs were found in 4 cases.Another 20 healthy volunteers were enrolled as control group,including 10 male and 10 female.The mean age was 31 years （range 24-50 years）.The ELISA method was used to detect the soluble MICA＇s （sMICA） level in serum.And the results were compared with tumor＇s malice,TNM pathology stages,metastasis.In 15cases with renal cell carcinoma,the expression of MICA molecule in tumor masses and paraneoplastic masses was measured by immunohistochemical （IHC） method.The quantitative expression of MICA-mRNA was detected by RT-PCR in 9 tumor masses and 3 paraneoplastic masses.Results The level of sMICA in renal malignant tumor group was （348.5±32.5） pg/ml,while the sMICA＇s level in benign renal tumor groups was （289.3±30.4） pg/ml and that in the control group was （168.4±43.2） pg/ml.The level of sMICA in malignant group is statistically higher than that in benign group and control group （P＜0.05）.The level of sMICA in T1 、T2 、T3 and T4 stage was （304.3±27.4）,（308.4±26.8）,（368.3±33.4）,（378.4±43.4） pg/ml,respectively.Insignificant difference only demonstrated between T1 and T2 stage.The level of sMICA in those patients with and without lymphatic metastasis was （326.2±32.4）,（319.4±32.5） pg/ml,respectively （P＞0.05）.Significant difference in the sMICA level could also be observed between patients with other organ metastasis （373.4±45.4） pg/ml and those without metastasis （346.4±31.5） pg/ml （P＜0.05）.The IHC results revealed that high expression of MICA molecule in tumor cell.However,this oppsite result was demonstrated in cells located in paraneoplastic tissues.In the results of RT-PCR,the MICA-mRNA level （2.03） in tumor masses was significantly higher than that in pareneoplastic masses （0.77） （P＜0.05）.Conclusions MICA highly expressed in renal tumor,and its expression correlates with tumor＇s malice,TNM pathologic stages,and metastasis.