食管鳞状细胞癌组织UL16结合蛋白3的表达和临床意义及与自然杀伤细胞的相关性

Expression and clinical significance of UL16 binding protein 3 in esophageal squamous cell carcinoma and its correlation with nature killer cells

目的研究UL16结合蛋白3（ULBP3）在食管鳞状细胞癌组织中的表达和临床意义及与NK细胞的相关性。方法应用实时荧光定量PCR、免疫组织化学染色法以及Western印迹技术检测40份食管鳞状细胞癌组织和相应癌旁组织中ULBP3的相对表达，并运用流式细胞术检测同一患者外周血中NK细胞的百分比，Pearson法分析NK细胞百分比与ULBP3之间的关系。结果40份食管鳞状细胞癌组织中，ULBP3mRNA的相对表达量显著高于相应癌旁组织[（4．96±6．11）×10^-3比（1．64±2．96）×10^-3，t=3．656，P〈0．01]。免疫组织化学结果显示ULBP3蛋白在60％（24／40）的食管鳞状细胞癌组织中呈阳性而在癌旁组织中仅有32．5％（13／40）阳性（t=3．921，P〈0．01）。Western印迹结果显示食管鳞状细胞癌组织中ULBP3蛋白表达量较相应癌旁组织丰富；淋巴结有转移者和TNMIII期患者肿瘤组织的ULBP3mRNA相对表达量高于无转移及Ⅰ和Ⅱ期组织（t=4．839，4．192，P〈0．05），而与年龄、性别、肿瘤位置、分化程度无明显相关性（P〉0．05）。在肿瘤的早中期，ULBP3mRNA的表达量与外周血NK细胞的含量呈正相关（r=0．5233，P〈0．05），但在晚期肿瘤中无明显相关性。结论ULBP3在食管鳞状细胞癌中高表达，并可能参与了NK细胞的免疫调节。

Objective To investigate the expression and clinical significance of UL16 binding protein 3 （ULBP3） in human esophageal squamous cell carcinoma （ESCC） and its correlation with nature killer （NK） cells. Methods The relative expression of ULBP3 in the ESCC tissues and corresponding carcinoma adjacent tissues of 40 patients was detected by realtime-poly merase chain reaction （PCR）, immunohistochemical staining and Western blot methods. The percentage of NK cells in peripheral blood of same patients was examined by flow cytometry. The correlation between ULBP3 and the percentage of NK ceils was analyzed with Pearson method. Results The expression of ULBP3 at mRNA level in the tumor tissues （[4. 96 ± 6. 11]×10^-3） was significantly higher than that of corresponding carcinoma adjacent tissues （[1. 64±2. 96]× 10^-3, t= 3. 656, P〈0. 01）. The immunohistochemical staining results indicated that the positive rate of ULBP3 in the tumor tissues was 60% （24/40）, however that of corresponding carcinoma adjacent tissues was only 32. 5%（13/40, t=3. 921, P〈0. 01）. The Western blot results indicated that the expression of ULBP3 at protein level in the tumor tissues was significantly higher than that in the corresponding carcinoma adjacent tissues. The relative expresssion ULBP3 at mRNA level in carcinoma tissues of ESCC patients with lymph node metastasis and at TNM stage III was higher than that of ESCC patients without metastasis and at TNM stage Ⅰ and Ⅱ （t= 4. 839, 4. 192, P〈0.05）. There was no significant correlation between the expression and ages, gender, location of tumors and the differentiation degree of tumor （P〉0.05）. At early and mid stage of the tumor, the expression of ULBP3 at mRNA level was positively correlated with the percentage of NK cells in peripheral blood （r=0. 5233, P〈0.05）, however there was no correlation at advanced stage. Conclusion ULBP3 was highly expressed in ESCC and may be involved in the immune regulation of NK cells.