miR-196和HoxB8与结直肠癌Folfox4化疗敏感性的相关研究

MiR-196 and HoxB8 Influence on The Sensitivity of Neoadjuvant Chemotherapy with Folfox4 Scheme in Colorectal Cancer

目的探讨结直肠癌患者术前接受Folfox4方案化疗对miR-196和HoxB8表达的影响,并探讨miR-196和HoxB8在结直肠癌组织中的表达差异以及与Folfox4方案化疗敏感性的相关性及其意义。方法分别用荧光定量PCR技术和免疫组化技术检测新辅助化疗组(包括化疗敏感组与不敏感组)和未化疗组患者结直肠癌组织中miR-196和HoxB8的表达情况,分析二者在不同组间的表达差异及其相关性。结果结直肠癌组织中miR-196和HoxB8 mRNA的相对表达量在新辅助化疗组分别为0.646 8±0.683 9和0.607 6±0.418 9,相比未化疗组的1.000 0±0.000 0和1.000 0±0.000 0均下降(P<0.01);miR-196在化疗敏感组的表达相对量为0.948 9±0.691 0,高于不敏感组的0.344 7±0.536 1(P<0.01);HoxB8 mRNA在化疗敏感组的表达相对量为0.489 9±0.371 5,低于不敏感组的0.725 3±0.437 5(P<0.05);免疫组化结果提示化疗敏感组中HoxB8蛋白表达阳性率低于不敏感组(Z=-2.396,P=0.017)。在新辅助化疗组和未化疗组中,miR-196和HoxB8 mRNA的表达均存在负相关关系(r=-0.595,P<0.01;r=-0.435,P<0.01)。结论术前Folfox4方案化疗可以降低miR-196和HoxB8在结直肠癌组织中的表达水平;miR-196和HoxB8的表达差异可能与结直肠癌患者对Folfox4方案的化疗敏感性相关,高表达的miR-196可能通过抑制HoxB8的表达水平从而增强Folfox4化疗的敏感性。

Objective To explore the influence of patients who accepted chemotherapy of Folfox4 scheme before operation for the expression of miR-196 and HoxB8 in colorectal cancer, and illustrating the differences between the miR- 196 and HoxB8 expressions in colorectal cancer tissues and sensitivity to chemotherapy with Folfox4 scheme and its corre- lation and significance. Methods Fluorescence quantitative PCR （RT-PCR） and immunohistochemistry were used to determine the expressions of miR-196 and HoxB8 in 50 specimens of neoadjuvant chemotherapy group （chemotherapy sensitive group and chemotherapy insensitive group） and 30 specimens which received the surgery directly （no-chemo- therapy group）, and analyzing the relationship and discrepancy between miR-196 and HoxB8 in these groups. Results The RT-PCR examination showed that the relative expression levels of miR-196 and HoxB8 in the neoadjuvant chemo- therapy group were lower than the no-chemotherapy group （0. 646 8±0. 683 9 vs. 1. 000 0±0. 000 0, P〈0. 01 ; 0. 607 6± 0.418 9 vs. 1. 000 0±0. 000 0, P〈0. 01）. Expression of miR-196 in the chemotherapy sensitive group was higher than the chemotherapy insensitive group （0. 948 9±0. 691 0 vs. 0. 344 7±0. 536 1, P〈0. 01）, however, the expression of HoxB8 mRNA in the chemotherapy sensitive group was lower than the chemotherapy insensitive group （0. 489 9± 0. 371 5vs. 0. 725 3±0. 437 5, P 〈 0. 05）. Expression positive rate of HoxB8 protein in chemotherapy sensitive group was lower than the chemotherapy insensitive group （Z=-2. 396, P=0. 017）. The expressions ofmiR-196 and HoxB8 in the neoadjuvant chemotherapy group had negative relationship （r=-0. 595, P〈0. 01）, which was also exist in the no-chemo- therapy group （r=--0. 435, P〈0.01）. Conclusions The neoadjuvant chemotherapy with Folfox4 scheme before oper- ation can reduce the expression levels ofmiR-196 and HoxB8 in colorectal cancer tisssues. The different expression levels of miR-196 and HoxB8 could influence the sensitivity of neoadjuvant chemotherapy with Folfox4 scheme in colorectal cancer. The high level expression of miR-196 could restrain the expression of HoxB8, and then increase the sensitivity of chemotherapy with Folfox4 scheme in colorectal cancer.