B细胞特异的莫洛尼白血病病毒插入位点1基因蛋白在结肠癌中的表达及其意义

Expression and clinicophathological significance of Bmi-1 oncoprotein in colon cancer

目的探讨B细胞特异的莫洛尼白血病病毒插入位点1基因（Bmi-1）的表达对结肠癌临床诊断及预后的意义。方法逆转录-聚合酶链反应（RT—PCR）检测Bmi-lmRNA在癌组织及癌旁黏膜中的表达差异。免疫组织化学研究203例结肠癌癌组织、203例癌旁正常黏膜和66例癌转移淋巴结中Bmi-1的表达，分析Bmi。1与临床病理特征和预后的相关性。结果RT-PCR显示结肠癌中Bmi-1mRNA表达显著高于癌旁正常黏膜。免疫组织化学结果显示癌旁正常黏膜、癌组织和癌转移淋巴结中的表达率分别为7．9％、66．6％、86．4％。Bmi-1过表达与临床分期、浸润深度、淋巴结转移和远处转移相关。Kaplan—Meier分析显示Bmi—1阳性组的无病生存时间和总生存时间较阴性组显著减低。COX回归多因素分析显示Bmi-1是影响结肠癌预后的独立因素之一（P〈0．05）。结论Bmi—1过度表达可能参与结肠癌的发生发展过程。

Objective To investigate the clinicophathological significance and predictive value of the expression of Bmi-1 （ B-cell specific moloney leukemia virus insertion site 1 ） gene in colon cancer. Methods Bmi-1 expression was assessed by immunohistochemistry in a tissue microarray （TMA） containing 203 cases of primary colon cancer paired with 203 non-cancerous tissue and available 66 lymph node metastasis （LNM）. Reverse transcription-PCR was performed to detect the mRNA levels of Bmi-1 in colon cancer. Results The statistical analysis showed 16 （7.9%） ,133 （66.6%） and 57 （86.4%） staining positivity for Bmi-1 in non-cancerous tissue, colon cancer and metastases, respectively. Overexpression of Bmi-1 was significandy correlated with clinical stage （P 〈0.01 ） ,depth of invasion （P 〈0.01 ） ,nodal involvement （ P 〈 0.01 ）, distant metastasis （ P 〈 0.05 ）. RT-PCR indicated Bmi-1 mRNA was up-regulated in the colon cancer tissue relative to normal colonic mucosa. Patients positive for Bmi-l-had a much lower 5-year disease-free survival （P 〈 O. O1 ） and overall survival （P 〈 O. O1 ） than those negative for Bmi-1. Bmi-1 immunoreactivity emerged as an independent prognostic factor in the multivariate analysis. Conclusion The overexpression of Bmi-1 may be involved in the incidence and development of colon cancer.