预测新疆不同民族局部晚期食管鳞癌放化疗疗效的血清microRNA初步筛选

发布时间：2018-03-21 11:03

  本文选题：食管鳞癌　切入点：民族　出处：《新疆医科大学》2017年博士论文　论文类型：学位论文

【摘要】：目的:通过对汉族、维吾尔族及哈萨克族局部晚期食管鳞癌患者放化疗前后血清microRNA的检测及比较;放化疗敏感组及抗拒组血清microRNA的比对,探讨不同民族血清差异表达microRNA的表达特征;评价血清microRNA预测放化疗近期疗效的价值。方法:1、收集局部晚期食管鳞癌患者共30例,进行同步放化疗,同时采集患者放化疗前、后的外周血及正常体检者外周血作为对照组,疗效评价及随访。2、用Agilent microRNA人类基因芯片进行microRNA检测;DIANA-mirPath.v3进行生物学功能的预测及RT-qPCR定量及验证。结果:1、近期疗效随访结果:CR+PR为治疗敏感组,共14例;SD+PD为治疗抵抗组,共16例。2、放化疗前后血清microRNA差异表达特征:(1)放化疗前有98个microRNA差异表达显著,放化疗后有81个microRNA差异表达显著;放化疗后较放化疗前有1个microRNA差异表达显著,为miR-623;(2)放化疗前后所有筛选出的microRNA差异表达倍数达3倍以上的有4个:miR-150-5p、miR-486-5p、miR-16-5p、miR-3185;(3)通过KEGG通路分析显示,miR-623可能参与NF-kappa B信号通路调节。3、不同民族血清microRNA的差异表达特征:(1)汉族放化疗前共有160个microRNA差异表达显著,放化疗后共有124个microRNA差异表达显著,放化疗后对比放化疗前共有6个microRNA差异表达显著;(2)维吾尔族放化疗前有92个microRNA表达显著异常,放化疗后共有103个microRNA表达显著异常,放化疗后对比放化疗前共有2个microRNA表达显著异常;(3)哈萨克族放化疗前有115个microRNA差异表达显著,放化疗后有129个microRNA差异表达显著,放化疗后组对比放化疗前组共有4个microRNA差异表达显著;(4)三个民族血清microRNA的差异表达比较结果:哈萨克族与汉族共有6个microRNA差异表达显著;哈萨克族与维吾尔族共有10个microRNA差异表达显著;维吾尔族与汉族共有17个microRNA差异表达显著;三个民族中两两比较差异表达显著的是miR-4454,miR-144-3p,miR-4459。3、局部晚期食管鳞癌放化疗敏感组与抗拒组比较,有11个microRNA差异表达显著,其中miR-623、miR-5703及miR-483-5p经RT-qPCR验证后差异显著更明显。ROC曲线预测miR-623与食管鳞癌放化疗近期疗效的曲线下面积(AUC)、灵敏度和特异度分别为0.809、72.2%、82.0%;miR-5703分别为0.928、91.7%、90.0%;miR-483-5p分别为0.838、69.4%、90.0%。结论:1、食管鳞癌患者的血清中可以检测到与食管癌诊断及放化疗敏感性相关的microRNA;2、汉族、维吾尔族、哈萨克族三民族食管癌之间血清microRNA存在差异表达;3、miR-623、miR-5703、miR-483-5p对于食管鳞癌放化疗具有疗效预测价值。
[Abstract]:Objective: to compare the detection and comparison of serum microRNA before and after radiotherapy and chemotherapy in local advanced esophageal squamous cell carcinoma patients of Han, Uygur and Kazak nationalities, and to compare the serum microRNA levels between chemoradiosensitive group and chemosensitive group. To evaluate the value of serum microRNA in predicting the short-term curative effect of radiotherapy and chemotherapy, 30 patients with locally advanced esophageal squamous cell carcinoma were collected for simultaneous radiotherapy and chemotherapy. The peripheral blood of the patients with normal physical examination was used as the control group. The biological function of DIANA-mirPath.v3 was predicted by Agilent microRNA human gene chip, and the RT-qPCR quantification and verification were performed. Results: 1. The short-term follow-up results showed that: CR was the sensitive group, and 14 patients were treated with SD PD as the resistant group. There were 98 microRNA and 81 microRNA differentially expressed before radiotherapy and chemotherapy, 1 microRNA after radiotherapy and chemotherapy, and 1 microRNA after radiotherapy and chemotherapy. 4: miR-150-5pnmiR-486-5pnmiR-16-5pnmiR-3185 ~ 3) the KEGG pathway analysis showed that miR-623 may be involved in the regulation of NF-kappa B signaling pathway. The differential expression characteristics of microRNA in different ethnic groups were: 1). (1) the differential expression characteristics of microRNA in different ethnic groups were as follows: 1) in Han nationality, the differential expression of miR-623 might be involved in the regulation of NF-kappa B signaling pathway by means of KEGG pathway analysis. There were 160 microRNA differentially expressed before radiotherapy and chemotherapy. There were 124 microRNA differentially expressed in Uygur patients after radiotherapy and chemotherapy, and 6 microRNA differentially expressed after radiotherapy and chemotherapy. There were 92 abnormal microRNA expression in Uygur before radiotherapy and chemotherapy, and 103 microRNA in Uygur before radiotherapy and chemotherapy. There were two abnormal expressions of microRNA in Kazak before radiotherapy and chemotherapy. There were 115 microRNA differentially expressed in Kazak before radiotherapy and chemotherapy, and 129 microRNA in Kazak before radiotherapy and chemotherapy. The difference of microRNA expression in serum of three nationalities was as follows: there were 6 microRNA differentially expressed in Kazak and Han nationality. There were 10 microRNA differentially expressed in Kazak and Uygur, 17 microRNA in Uygur and Han. The difference in expression of miR-4454miR-144-3pnmiR-4459.3 was significant among the three ethnic groups. There were 11 microRNA differentially expressed in chemosensitive and chemosensitive groups of locally advanced esophageal squamous cell carcinoma compared with resistance-resistant group. The difference between miR-623mmiR-5703 and miR-483-5p was more obvious after RT-qPCR verification. ROC curve was used to predict the area under the curve of short-term curative effect of radiotherapy and chemotherapy for miR-623 and esophageal squamous cell carcinoma. The sensitivity and specificity of miR-5703 were 0.80972.2and 82.0miR-5703 were 0.92891.70.090.0MiR-483-5p were 0.838 / 69.45.Conclusion\\\;\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%? MicroRNAs associated with the diagnosis of esophageal cancer and sensitivity to radiotherapy and chemotherapy were detected in the Han nationality. The difference of serum microRNA expression between Uygur and Kazak nationalities was significant in predicting the curative effect of radiotherapy and chemotherapy for esophageal squamous cell carcinoma (ESCC) with different expression of miR-623 miR-5703 miR-483-5p.
【学位授予单位】：新疆医科大学
【学位级别】：博士
【学位授予年份】：2017
【分类号】：R735.1

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