miR-196和HoxB8与结直肠癌Folfox4化疗敏感性的相关研究

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HoxB8mRNA的相对表达量在新辅助化疗组分别为0．6468±0．6839和0．6076±0．4189，相比未化疗组的1．0000±0．0000和1．0000±0．0000均下降（P〈0．01）；miR-196在化疗敏感组的表达相对量为0．9489±0．6910，高于不敏感组的0．3447±0．5361（P〈0．01）；HoxB8mRNA在化疗敏感组的表达相对量为0．4899±0．3715，低于不敏感组的0．7253±0．4375（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HoxB8mRNA的表达均存在负相关关系驴-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。

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

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.