本文選題：宮頸鱗癌 + miR-196a��； 參考：《廣西醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的探討miR-196a及其靶基因HoxB8 mRNA在不同宮頸癌細(xì)胞株中的表達(dá)情況,HoxB8基因?qū)m頸癌細(xì)胞凋亡的影響;探討HoxB8蛋白在宮頸鱗癌組織中的表達(dá)及臨床意義。方法1.通過(guò)實(shí)時(shí)熒光定量PCR檢測(cè)宮頸癌Caski、SiHa、C33-A和HeLa細(xì)胞系中miR-196a和HoxB8 mRNA的表達(dá)情況;通過(guò)q RT-PCR檢測(cè)miR-196a模擬物轉(zhuǎn)染宮頸癌SiHa細(xì)胞后對(duì)HoxB8表達(dá)的影響;通過(guò)HoxB8 siRNA瞬時(shí)轉(zhuǎn)染宮頸癌SiHa細(xì)胞后檢測(cè)Caspase3/7的活性;2.收集整理廣西醫(yī)科大學(xué)附屬腫瘤醫(yī)院婦瘤科2011年2月至2012年12月行宮頸活檢術(shù)67例HPV16(+)IIb-IIIb期宮頸鱗癌放化療或放療病例的臨床病理資料,并在病理科標(biāo)本庫(kù)找出其石蠟標(biāo)本。通過(guò)免疫組化染色的方法研究HoxB8的表達(dá)情況,并進(jìn)一步分析其與各臨床病理因素及預(yù)后的關(guān)系。用卡方檢驗(yàn)或Fisher精確檢驗(yàn)進(jìn)行與臨床病理因素間相關(guān)性比較,Kaplan-Meier法計(jì)算生存率,Log-rank法進(jìn)行生存曲線比較,Cox回歸模型進(jìn)行多因素分析。結(jié)果1.實(shí)時(shí)熒光定量PCR結(jié)果顯示,miR-196a在HPV16陽(yáng)性的Caski和SiHa細(xì)胞系中的表達(dá)明顯低于HPV16陰性的C33-A和HeLa,差異具有統(tǒng)計(jì)學(xué)意義(P0.001);與之相對(duì)應(yīng)的,HoxB8在HPV16陽(yáng)性的Caski和SiHa細(xì)胞系中的表達(dá)則明顯高于HPV16陰性的C33-A和HeLa,差異具有統(tǒng)計(jì)學(xué)意義(P0.001);miR-196a可下調(diào)HoxB8的表達(dá);Capase3/7活力檢測(cè)結(jié)果顯示,Capase3/7活力在SiHa細(xì)胞HoxB8 si RNA轉(zhuǎn)染組明顯高于陰性對(duì)照組和正常對(duì)照組,差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。2.HoxB8陰性10例,陽(yáng)性57例(85%)。染色結(jié)果與各臨床病理因素相關(guān)性分析顯示HoxB8與年齡、腫瘤最大徑、治療前SCC、分化程度、FIGO分期均無(wú)統(tǒng)計(jì)學(xué)意義。67例患者失訪率19.4%,中位總生存時(shí)間為48個(gè)月,1年、3年、5年總生存率分別為91%、66%和54%。單因素及多因素生存分析顯示,腫瘤最大徑4cm、單純放療是IIb-IIIb宮頸鱗癌患者預(yù)后不良的獨(dú)立危險(xiǎn)因素,差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論miR-196a可能通過(guò)下游靶基因HoxB8影響宮頸癌細(xì)胞凋亡;HoxB8與HPV16(+)IIb-IIIb期宮頸鱗癌患者年齡、腫瘤最大徑、治療前SCC、分化程度、FIGO分期無(wú)明顯相關(guān)性;腫瘤最大徑4cm、單純放療HPV16(+)IIb-IIIb宮頸鱗癌患者總生存時(shí)間縮短,腫瘤最大徑、治療方式是影響OS的獨(dú)立危險(xiǎn)因素;HoxB8與HPV16(+)IIb-IIIb期宮頸鱗癌患者預(yù)后無(wú)明顯相關(guān)性。
[Abstract]:Objective to investigate the expression of miR-196a and its target gene HoxB8 mRNA in different cervical cancer cell lines and the effect of HoxB8 gene on apoptosis of cervical cancer cells, and to explore the expression and clinical significance of HoxB8 protein in cervical squamous cell carcinoma. Method 1. The expression of miR-196a and HoxB8 mRNA in the cervical cancer cell lines Caskius SiHaC33-A and HeLa was detected by real-time fluorescence quantitative PCR, and the effect of miR-196a mimics on HoxB8 expression in cervical cancer SiHa cells was detected by Q RT-PCR. The activity of Caspase3/7 was detected by transient transfection of HoxB8 siRNA into cervical cancer SiHa cells. The clinicopathological data of 67 cases of HPV16 (stage IIb-IIIb) cervix squamous cell carcinoma treated with radiotherapy, chemotherapy or radiotherapy from February 2011 to December 2012 were collected and analyzed. The paraffin specimens were found in the specimen bank of pathology department. Immunohistochemical staining was used to study the expression of HoxB8 and its relationship with clinicopathological factors and prognosis. The correlation between clinical and pathological factors was compared by chi-square test or Fisher accurate test. Kaplan-Meier method was used to calculate survival rate and Log-rank method was used to compare survival curve and Cox regression model was used for multivariate analysis. Result 1. The results of real-time fluorescence quantitative PCR showed that the expression of miR-196a in HPV16 positive Caski and SiHa cell lines was significantly lower than that in HPV16 negative C33-A and HeLa cells, the difference was statistically significant (P0.001), and the corresponding expression of HoxB8 in HPV16 positive Caski and SiHa cell lines was significantly lower than that in HPV16 negative Caski and SiHa cell lines. It was significantly higher than that of C33-A and HeLa-negative HPV16, and the difference was statistically significant. P0.001 miR-196a could down-regulate the expression of HoxB8 and Capase3 / 7 activity. The results showed that the activity of capase3 / 7 in SiHa cell HoxB8 si RNA transfection group was significantly higher than that in SiHa cell HoxB8 si RNA transfection group and normal control group. The difference was statistically significant (P 0.05) .2.HoxB8 was negative in 10 cases and positive in 57 cases (85%). The correlation analysis between staining results and clinicopathological factors showed that HoxB8 was associated with age and the maximum diameter of tumor. There was no significant difference in SCC, differentiation and Figo stage before treatment. The median survival time was 48 months, 1 year, 3 years and 5 years. The overall survival rate was 91 66% and 54% respectively. Univariate and multivariate survival analysis showed that the maximum diameter of the tumor was 4 cm and radiotherapy alone was an independent risk factor for poor prognosis in patients with IIb-IIIb cervical squamous cell carcinoma. The difference was statistically significant (P 0.05). Conclusion miR-196a may affect apoptosis of cervical cancer cells by downstream target gene HoxB8. There is no significant correlation between HoxB8 and HPV16 (stage IIb-IIIb) cervical squamous cell carcinoma patients age, tumor maximum diameter, pre-treatment SCC, differentiation degree and Figo stage. The maximum diameter of tumor was 4 cm, the total survival time of patients with cervical squamous cell carcinoma of HPV16 was shortened and the maximum diameter of tumor was shortened by radiotherapy alone. The independent risk factor of affecting OS was HoxB8 and the prognosis of patients with squamous cell carcinoma of cervix of HPV16 was not significantly correlated with that of HPV16 (stage IIb-IIIb).
【學(xué)位授予單位】：廣西醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R737.33

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 商文靜;龐敏;劉越;;高分辨率溶解曲線分析miRNA-196a2基因多態(tài)性與肺癌相關(guān)性[J];濱州醫(yī)學(xué)院學(xué)報(bào);2016年02期

2 丁波;王美林;張正東;韓素萍;;miR-196a2 T>C基因多態(tài)與宮頸癌易感性的關(guān)系研究[J];南京醫(yī)科大學(xué)學(xué)報(bào)(自然科學(xué)版);2016年01期

3 馮強(qiáng);黃翔;;miRNA-32、-196a、-218和-128與let7i在前列腺癌患者血清中的表達(dá)及意義[J];廣東醫(yī)學(xué);2016年01期

4 Manish K.Pal;Shyam P.Jaiswar;Vinaya N.Dwivedi;Amit K.Tripathi;Ashish Dwivedi;Pushplata Sankhwar;;MicroRNA: a new and promising potential biomarker for diagnosis and prognosis of ovarian cancer[J];Cancer Biology & Medicine;2015年04期

5 林飛燕;吳愛(ài)華;張培麗;蔣磊;李紹堂;;HoxB8對(duì)結(jié)直腸癌細(xì)胞生長(zhǎng)遷移的影響[J];溫州醫(yī)科大學(xué)學(xué)報(bào);2015年11期

6 徐鄭;竇全亮;賈瑞鵬;朱佳庚;;miRNA-196a2及miRNA-499基因多態(tài)性與膀胱癌的相關(guān)性研究[J];醫(yī)學(xué)研究生學(xué)報(bào);2015年03期

7 高冬梅;朱明s，

本文編號(hào)：1970224