遗传性非息肉病性结直肠癌中COX-2的表达及与MMR基因表达的分析

摘要

目的 研究遗传性非息肉病性结直肠癌(HNPCC)中环氧合酶2(COX-2)的表达及与错配修复基因(MMR)的关系.方法 选择2008年5月~2011年10月19个家系的家族遗传性非息肉病性大肠癌20例;选择同期本院收治的散发性大肠癌23例为对照组,采用免疫组化及PCR技术检测两组患者COX-2表达及MMR基因表达情况.结果 HNPCC大肠癌中COX-2高表达率为40.0%,散发性大肠癌中COX-2的高表达率为91.3%,两组比较差异有统计学意义(χ2 = 10.172,P < 0.05).HNPCC大肠癌中MMR表达缺失率为70%,散发性大肠癌中MMR表达缺失率为13%,两组比较差异有统计学意义(χ2 = 9.872,P < 0.05).MMR表达缺失的遗传性大肠癌及散发性大肠癌COX-2高表达率(21.4%、66.7%)均明显低于MMR阳性表达者(83.3%、95.0%),差异有统计学意义(χ2 = 7.357、5.039,P < 0.05).相关性分析显示,HNPCC大肠癌MMR表达缺失率与COX-2低表达率呈正相关(r = 1.176,P < 0.05),散发性大肠癌患者中,MMR表达率与COX-2高表达率呈正相关(r = 1.869,P < 0.05).结论 遗传性非息肉病性结直肠癌中COX-2的表达较散发性大肠癌减低,MMR基因表达缺失率增高,COX-2、MMR基因表达情况在遗传性非息肉型结直肠癌的筛查及发病机制的研究中有重要意义.%Objective To study the relationship between the expression of cyclooxygenase-2 (COX-2) and the mismatch repair (MMR) genes in hereditary nonpolyposis colorectal cancer (HNPCC). Methods 20 patients with HNPCC from 19 pedigrees from May 2008 to October 2011 were selected, and 23 patients with sporadic colorectal cancer treated in our hospital in the same period were selected as the control group. The immunohistochemistry and PCR techniques were used to detect the COX-2 expression and MMR gene expression of the two groups. Results The high expression rate of COX-2 was 40.0% in HNPCC colorectal cancer and 91.3% in sporadic colorectal cancer, with statistically significant difference between the two groups (x2 = 10.172, P < 0.05). The expression loss rate of COX-2 was 70% in HNPCC colorectal cancer and 13% in sporadic colorectal cancer, with statistically significant difference between the two groups (x2 = 9.872, P < 0.05). The high expression rate of COX-2 was 21.4% and 66.7% in the hereditary colorectal cancer and the sporadic colorectal cancer with MMR expression loss respectively, which were significantly lower than the 83.3% and 95.0% in those with MMR positive expression, with statistically significant differences (x = 7.357, 5.039, P < 0.05). Correlation analysis showed that the expression loss rate of MMR was positively correlated to the low expression rate of COX-2 (r = 1.869, P < 0.05) in the HNPCC colorectal cancer, and the expression rate of MMR was positively correlated to the high expression rate of COX-2 (r = 1.176, P < 0.05). Conclusion The HNPCC was lower than the sporadic colorectal cancer in the expression of COX-2, but higher in the expression rate of MMR gene. The expression of COX-2 and MMR gene are of important significance in the screening and pathogenesis of HNPCC.