預(yù)測新疆不同民族局部晚期食管鱗癌放化療療效的血清microRNA初步篩選
本文選題:食管鱗癌 切入點(diǎn):民族 出處:《新疆醫(yī)科大學(xué)》2017年博士論文 論文類型:學(xué)位論文
【摘要】:目的:通過對漢族、維吾爾族及哈薩克族局部晚期食管鱗癌患者放化療前后血清microRNA的檢測及比較;放化療敏感組及抗拒組血清microRNA的比對,探討不同民族血清差異表達(dá)microRNA的表達(dá)特征;評價(jià)血清microRNA預(yù)測放化療近期療效的價(jià)值。方法:1、收集局部晚期食管鱗癌患者共30例,進(jìn)行同步放化療,同時(shí)采集患者放化療前、后的外周血及正常體檢者外周血作為對照組,療效評價(jià)及隨訪。2、用Agilent microRNA人類基因芯片進(jìn)行microRNA檢測;DIANA-mirPath.v3進(jìn)行生物學(xué)功能的預(yù)測及RT-qPCR定量及驗(yàn)證。結(jié)果:1、近期療效隨訪結(jié)果:CR+PR為治療敏感組,共14例;SD+PD為治療抵抗組,共16例。2、放化療前后血清microRNA差異表達(dá)特征:(1)放化療前有98個(gè)microRNA差異表達(dá)顯著,放化療后有81個(gè)microRNA差異表達(dá)顯著;放化療后較放化療前有1個(gè)microRNA差異表達(dá)顯著,為miR-623;(2)放化療前后所有篩選出的microRNA差異表達(dá)倍數(shù)達(dá)3倍以上的有4個(gè):miR-150-5p、miR-486-5p、miR-16-5p、miR-3185;(3)通過KEGG通路分析顯示,miR-623可能參與NF-kappa B信號通路調(diào)節(jié)。3、不同民族血清microRNA的差異表達(dá)特征:(1)漢族放化療前共有160個(gè)microRNA差異表達(dá)顯著,放化療后共有124個(gè)microRNA差異表達(dá)顯著,放化療后對比放化療前共有6個(gè)microRNA差異表達(dá)顯著;(2)維吾爾族放化療前有92個(gè)microRNA表達(dá)顯著異常,放化療后共有103個(gè)microRNA表達(dá)顯著異常,放化療后對比放化療前共有2個(gè)microRNA表達(dá)顯著異常;(3)哈薩克族放化療前有115個(gè)microRNA差異表達(dá)顯著,放化療后有129個(gè)microRNA差異表達(dá)顯著,放化療后組對比放化療前組共有4個(gè)microRNA差異表達(dá)顯著;(4)三個(gè)民族血清microRNA的差異表達(dá)比較結(jié)果:哈薩克族與漢族共有6個(gè)microRNA差異表達(dá)顯著;哈薩克族與維吾爾族共有10個(gè)microRNA差異表達(dá)顯著;維吾爾族與漢族共有17個(gè)microRNA差異表達(dá)顯著;三個(gè)民族中兩兩比較差異表達(dá)顯著的是miR-4454,miR-144-3p,miR-4459。3、局部晚期食管鱗癌放化療敏感組與抗拒組比較,有11個(gè)microRNA差異表達(dá)顯著,其中miR-623、miR-5703及miR-483-5p經(jīng)RT-qPCR驗(yàn)證后差異顯著更明顯。ROC曲線預(yù)測miR-623與食管鱗癌放化療近期療效的曲線下面積(AUC)、靈敏度和特異度分別為0.809、72.2%、82.0%;miR-5703分別為0.928、91.7%、90.0%;miR-483-5p分別為0.838、69.4%、90.0%。結(jié)論:1、食管鱗癌患者的血清中可以檢測到與食管癌診斷及放化療敏感性相關(guān)的microRNA;2、漢族、維吾爾族、哈薩克族三民族食管癌之間血清microRNA存在差異表達(dá);3、miR-623、miR-5703、miR-483-5p對于食管鱗癌放化療具有療效預(yù)測價(jià)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.
【學(xué)位授予單位】:新疆醫(yī)科大學(xué)
【學(xué)位級別】:博士
【學(xué)位授予年份】:2017
【分類號】:R735.1
【參考文獻(xiàn)】
相關(guān)期刊論文 前10條
1 王瀾;李曉旭;韓春;劉麗虹;孔潔;朱龍玉;張安度;高超;李曉寧;田華;任雪姣;;食管癌長期生存患者臨床特征及治療相關(guān)因素分析[J];中華放射腫瘤學(xué)雜志;2016年06期
2 張彭南;孫紅;蔣紅元;;miR-483-5p在上皮性卵巢癌中的表達(dá)及其對順鉑敏感性的影響[J];中國癌癥雜志;2016年05期
3 李偉莉;王聞?wù)?王孝舉;;微小RNA對腫瘤耐藥性影響的研究狀況[J];中國臨床藥理學(xué)雜志;2016年07期
4 劉卓;歐陽勝榮;李媛媛;常會(huì)波;吳建新;;MicroRNA在腫瘤發(fā)生發(fā)展和診斷中作用的研究進(jìn)展[J];現(xiàn)代生物醫(yī)學(xué)進(jìn)展;2016年01期
5 Christine Kestens;Peter D Siersema;Jantine WPM van Baal;;Current understanding of the functional roles of aberrantly expressed micro RNAs in esophageal cancer[J];World Journal of Gastroenterology;2016年01期
6 張玉虹;李皓;劉陽晨;;miRNA在腫瘤放療敏感性中的作用及機(jī)制[J];現(xiàn)代腫瘤醫(yī)學(xué);2016年02期
7 Michael Hollis;Kavitha Nair;Arpita Vyas;Lakshmi Shankar Chaturvedi;Sahil Gambhir;Dinesh Vyas;;Micro RNAs potential utility in colon cancer: Early detection, prognosis, and chemosensitivity[J];World Journal of Gastroenterology;2015年27期
8 趙瑩瑩;邢卉春;;循環(huán)miRNA檢測方法研究進(jìn)展及其臨床應(yīng)用[J];中華實(shí)驗(yàn)和臨床感染病雜志(電子版);2015年01期
9 趙然;周鳴;王賀冉;熊煒;李小玲;李桂源;;MicroRNA參與腫瘤發(fā)生發(fā)展的調(diào)控機(jī)制[J];中南大學(xué)學(xué)報(bào)(醫(yī)學(xué)版);2013年12期
10 Bao-Zhong Li;Zhao-Li Chen;Su-Sheng Shi;Xiao-Li Feng;Xiao-Gang Tan;Fang Zhou;Jie He;;Overexpression of Cdc25C predicts response to radiotherapy and survival in esophageal squamous cell carcinoma patients treated with radiotherapy followed by surgery[J];Chinese Journal of Cancer;2013年07期
相關(guān)博士學(xué)位論文 前1條
1 韓高華;miRNA196a調(diào)控食管鱗癌Annexin A1蛋白表達(dá)對轉(zhuǎn)移和預(yù)后的影響及其機(jī)制研究[D];蘇州大學(xué);2015年
,本文編號:1643565
本文鏈接:http://sikaile.net/shoufeilunwen/yxlbs/1643565.html