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目的:探讨新疆维吾尔族和汉族乳腺癌组织中哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)及其下游分子4EBP1和S6K1的表达差异。方法:选取2005-03-01-2009-09-30新疆医科大学附属肿瘤医院的维吾尔族和汉族女性浸润性乳腺癌患者285例,使用免疫组化方法检测磷酸化mTOR及其下游分子4EBP1和S6K1的表达状况;分别选取2012-01-01-2012-06-30新疆医科大学附属肿瘤医院63例维、汉新鲜乳腺癌和癌旁组织样本,使用荧光定量RT-PCR法检测mTOR及其下游分子4EBP1和S6K1的mRNA表达状况。结果:免疫组化结果显示,维吾尔族和汉族p-mTOR在乳腺癌组织中的阳性表达率分别为77.1%和67.4%(P=0.067),在癌旁组织中的阳性表达率分别为57.6%和61.7%(P=0.485);p-4EBP1在癌组织中的阳性表达率分别为31.9%和20.0%(P=0.020),在乳腺癌旁组织中的阳性表达率分别是4.9%和12.1%(P=0.029);p-S6K1在癌组织中的阳性表达率分别为41.0%和43.3%(P=0.695),在乳腺癌旁组织中的阳性表达率分别为14.0%和22.7%,P=0.054;荧光定量RT-PCR结果显示,维、汉乳腺癌组织中mTOR mRNA相对定量结果差异有统计学意义,P=0.045;4EBP1和S6K1mRNA相对定量结果差异无统计学意义,P值分别为0.128和0.404。结论:mTOR信号通路中p-4EBP1的表达水平存在维、汉民族的差异,为研究维、汉不同民族之间乳腺癌差异及个体化治疗提供了进一步研究方向。mTOR及其下游分子mRNA表达水平与磷酸化蛋白的表达并不完全一致,提示蛋白表达的调控位点可能位于转录后水平。
Objective: To investigate the difference of mammalian target of rapamycin (mTOR) and its downstream molecules 4EBP1 and S6K1 in Uygur and Han nationality in Xinjiang Uygur and Han nationality. METHODS: A total of 285 Uygur and Han women with invasive breast cancer at the Affiliated Tumor Hospital of Xinjiang Medical University from March 2005 to January 2009 were selected for immunohistochemical detection of phosphorylated mTOR and its downstream molecules 4EBP1 and S6K1 Were selected from 2012-01-01 to 2012-06-30 Tumor Hospital of Xinjiang Medical University in 63 cases of Victoria and Han fresh breast cancer and paracancerous tissue samples were detected by real-time fluorescent quantitative RT-PCR mTOR and its downstream molecules 4EBP1 and S6K1 mRNA expression status. Results: Immunohistochemical results showed that the positive expression rate of p-mTOR in Uighur and Han nationality was 77.1% and 67.4% (P = 0.067), respectively. The positive rates of p-mTOR in breast cancer tissues were 57.6% And 61.7%, respectively (P = 0.485). The positive expression rate of p-4EBP1 in cancer tissue was 31.9% and 20.0% respectively (P = 0.020) (P = 0.029). The positive expression rate of p-S6K1 in cancer tissue was 41.0% and 43.3% respectively (P = 0.695), and the positive expression rates of p-S6K1 in paracancerous tissues were 14.0% and 22.7% 0.054. The results of quantitative RT-PCR showed that the relative quantification results of mTOR mRNA in the breast cancer tissues of Victoria and Han were statistically different (P = 0.045), while there was no significant difference between the relative quantification results of 4EBP1 and S6K1 mRNA (P = 0.128 and 0.404. CONCLUSION: The expression level of p-4EBP1 in mTOR signaling pathway is different from that in Han and Han ethnic groups. This study provides further research directions for the study of differences in breast cancer among different ethnic groups in Victoria and China and individualized treatment. The expression of mTOR and its downstream mRNA is not exactly the same as that of phosphorylated protein, suggesting that the regulatory sites of protein expression may be located at post-transcriptional level.