發(fā)布時(shí)間：2018-05-29 15:08

  本文選題：口腔鱗狀細(xì)胞癌 + 生存率　； 參考：《鄭州大學(xué)》2017年碩士論文

【摘要】：研究背景:口腔鱗狀細(xì)胞癌(oral squamous cell carcinoma,OSCC)又稱口腔鱗癌,是常見的發(fā)生于口腔頜面部的惡性腫瘤之一。盡管國內(nèi)外目前對口腔鱗癌的流行病學(xué)調(diào)查和回顧性研究層出不窮。但對于河南省本地區(qū)的相關(guān)研究為數(shù)不多。加強(qiáng)對河南地區(qū)口腔鱗癌患者發(fā)病特點(diǎn)及生存率等因素的研究,有利于提高全省在口腔鱗癌治療中的總體水平。micro RNA(mi RNA)是目前對于口腔鱗癌的研究熱點(diǎn)方向。研究證實(shí),mi RNA這類非編碼小RNA,是通過靶向、特異性作用m RNA或啟動因子,導(dǎo)致靶RNA降解或者抑制其翻譯,降低相關(guān)靶基因蛋白質(zhì)的表達(dá),從而發(fā)揮重要的生理和病理調(diào)控作用。目前研究已發(fā)現(xiàn),mi RNA的異常表達(dá)與疾病尤其是癌癥有著密切的關(guān)系。癌癥進(jìn)展中的一個(gè)關(guān)鍵步驟是增殖失控。最近有證據(jù)顯示mi RNA作為腫瘤癌基因或抑癌基因異常表達(dá)是影響腫瘤細(xì)胞生長的一個(gè)關(guān)鍵因素。在前期的基因芯片研究中我們已經(jīng)發(fā)現(xiàn)口腔鱗癌患者中mi RNA-602的高表達(dá)趨勢,并發(fā)現(xiàn)了EHMT1(常染色質(zhì)組蛋白甲基轉(zhuǎn)移酶1)基因可以通過甲基化組蛋白從而在轉(zhuǎn)錄水平抑制MAL基因的表達(dá),而mi R-602可對已經(jīng)發(fā)生轉(zhuǎn)錄的MAL m RNA進(jìn)一步發(fā)揮抑制作用,EHMT1/mi R-602轉(zhuǎn)錄本通過在轉(zhuǎn)錄水平及轉(zhuǎn)錄后水平協(xié)同影響MAL基因的穩(wěn)定性,從而對口腔鱗癌的轉(zhuǎn)移發(fā)揮調(diào)控作用。本研究擬對EHMT1在口腔鱗癌組織中的表達(dá)水平進(jìn)行探索,為口腔鱗癌的轉(zhuǎn)移尋找可靠的生物標(biāo)記物。目前對于口腔鱗狀細(xì)胞癌的標(biāo)準(zhǔn)化治療包括手術(shù)切除及隨后的輔助放療和化療。最近國內(nèi)外的研究在口腔鱗癌的綜合治療方面取得了一些進(jìn)展,但總體的預(yù)后情況仍然不太樂觀。新輔助化療(NACT)在口腔鱗癌治療中的作用,成為目前探索的重要領(lǐng)域。新輔助化療是指在實(shí)施局部治療方法(如手術(shù)或放療)前所做的全身化療,目的是使腫塊縮小、及早殺滅看不見的轉(zhuǎn)移細(xì)胞,以利于后續(xù)的手術(shù)、放療等治療[36-49]。其目的是減少手術(shù)切除的范圍,改善局部區(qū)域功能,控制和減少遠(yuǎn)端轉(zhuǎn)移,從而降低死亡率和復(fù)發(fā)率,改善治療結(jié)果。然而,新輔助化療在口腔癌中的適應(yīng)癥尚未明確定義,大多數(shù)研究未能顯示新輔助化療在可切除的口腔鱗癌中,對局部區(qū)域病變的控制和總體生存率的明顯影響。在一些對局部病變晚期和不可切除口腔鱗癌的病人的研究中,新輔助化療可以顯著的控制腫瘤的生長,縮小病變的范圍并給手術(shù)切除創(chuàng)造機(jī)會。盡管這些研究闡述了新輔助化療對極晚期和不可切除的口腔鱗癌,遠(yuǎn)端轉(zhuǎn)移和可切除性及預(yù)后功能的一些積極影響,但需要進(jìn)一步驗(yàn)證。目前臨床上主要通過氟尿嘧啶、順鉑、阿霉素等藥物進(jìn)行化療治療,但這些藥物在發(fā)揮抗癌作用的同時(shí)易產(chǎn)生耐藥性,而且毒副作用很大。因此,急需找到一個(gè)新型的有效的抗腫瘤藥物以提高患者的生存率。砷劑(主要是亞砷酸鈉,Na As O2)在血液系統(tǒng)腫瘤方法有較多的研究,在胃癌、肺癌等實(shí)體腫瘤中也有研究,但總體研究較少,且對口腔鱗狀細(xì)胞癌的研究尚不明確。因此,本研究檢測亞砷酸鈉對體外培養(yǎng)的人口腔鱗狀細(xì)胞癌HN12細(xì)胞增殖凋亡的影響,并探討其機(jī)制,以期為亞砷酸鈉的臨床影響提供理論基礎(chǔ)。第一部分:對河南地區(qū)461例口腔鱗癌患者的回顧性分析目的:通過對2007年至2012年在鄭州大學(xué)第一附屬醫(yī)院口腔頜面外科就診的口腔鱗癌患者的病例資料進(jìn)行搜集和整理,總結(jié)河南地區(qū)口腔鱗癌發(fā)病的特點(diǎn)。分析與口腔鱗癌發(fā)病及預(yù)后生存率和復(fù)發(fā)率相關(guān)的因素。為河南地區(qū)口腔鱗癌患者的治療方法選擇和復(fù)發(fā)的預(yù)防以及預(yù)后的評估提供參考。方法:搜集和整理2007年至2012年于鄭州大學(xué)第一附屬醫(yī)院口腔頜面外科住院手術(shù)治療的口腔鱗癌患者的病歷資料,用SPSS21.0,Graph Pad6.0等統(tǒng)計(jì)軟件對納入的患者病例資料進(jìn)行統(tǒng)計(jì)學(xué)分析,分別統(tǒng)計(jì)患者的年齡、性別、地域、腫瘤分化程度、病理TNM分期等特點(diǎn)。研究對象為符合篩選條件的河南地區(qū)口腔鱗癌患者,對研究中涉及到的復(fù)發(fā)率分析采用卡方檢驗(yàn)進(jìn)行數(shù)據(jù)分析。選擇α=0.05作為檢驗(yàn)水準(zhǔn),當(dāng)P0.05認(rèn)為具有統(tǒng)計(jì)學(xué)意義。在對影響術(shù)后生存時(shí)間的因素的研究中,采用Kaplan-Meier生存分析法繪制生存曲線,并使用Log-rank法對所得出的數(shù)據(jù)進(jìn)行檢驗(yàn)。結(jié)果:1河南地區(qū)461例口腔鱗癌患者的基本情況分析在461名口腔鱗癌患者中男性280人,女性181人;發(fā)病年齡主要集中在50-79歲;鄭州市就診患者顯著高于其他地區(qū)患者,另外豫西北地區(qū)三門峽市、濟(jì)源市、鶴壁市、洛陽市就診患者分布數(shù)量較少,相比而言豫東地區(qū)周口市、開封市、商丘市就診患者分布相對較多;就診患者中,中-高分化的口腔鱗癌患者占大多數(shù);從發(fā)病部位上看,就診患者中舌,頰粘膜,牙齦發(fā)病率位列前三。2.對95例河南地區(qū)口腔鱗癌患者的復(fù)發(fā)率及生存率分析在前期研究中的461例患者中隨機(jī)選取95例符納入標(biāo)準(zhǔn)的病例進(jìn)行后續(xù)研究。觀察到這些患者的復(fù)發(fā)率和生存率研究中,年齡、腫瘤的臨床分期對生存率產(chǎn)生影響;研究中還觀察到腫瘤的分化程度和腫瘤的臨床分期對復(fù)發(fā)率可以產(chǎn)生影響;對于晚期(IV期)的患者而言輔助化療對患者的生存率存在影響;對于分化程度較低的口腔鱗癌患者輔助化療對患者的復(fù)發(fā)率存在影響。小結(jié):1河南地區(qū)口腔鱗癌患者發(fā)病特點(diǎn)研究表明,口腔鱗癌在河南地區(qū)的分布存在地域差異。造成這一現(xiàn)象的原因可能主要有交通條件差異,各地市級醫(yī)院或基層醫(yī)院的醫(yī)療條件差異等。從本研究的結(jié)果中觀察到,河南地區(qū)口腔鱗癌的發(fā)病特點(diǎn)與全國基本相符。但在發(fā)病年齡段上,位于70-79歲的患者數(shù)量也尤為突出,而造成這一結(jié)果的具體因素還有待進(jìn)一步研究。在這些患者中分化程度較低的患者數(shù)量較少,這可能與Broders/WHO組織學(xué)分級系統(tǒng)本身存在的固有缺陷有關(guān)。2影響口腔鱗癌術(shù)后復(fù)發(fā)率的相關(guān)因素本研究結(jié)果顯示,就研究所涉及的口腔鱗癌患者而言,年齡,性別對口腔鱗癌的復(fù)發(fā)率沒有影響。而在研究中觀察到,病理分級和臨床分期對口腔鱗癌的術(shù)后復(fù)發(fā)率存在影響。對于低分化口腔鱗癌的患者而言,化療對其術(shù)后復(fù)發(fā)率也存在著影響。3影響口腔鱗癌術(shù)后生存率的相關(guān)因素研究發(fā)現(xiàn)對于口腔鱗癌患者而言年齡和腫瘤的臨床分期可能是影響患者術(shù)后生存率的因素。高年齡組的患者術(shù)后生存時(shí)間低于低年齡組,I期患者的術(shù)后生存率高于IV期患者。研究同時(shí)還發(fā)現(xiàn)對于晚期(IV期)口腔鱗癌患者而言,接受化療有助于改善患者的術(shù)后生存率。提示我們對于晚期患者的輔助化療在晚期口腔鱗癌的治療領(lǐng)域仍然值得研究。第二部分:EHMT1在口腔鱗癌組織中的表達(dá)目的:了解EHMT1在口腔鱗癌組織中的表達(dá)情況,探究EHMT1的表達(dá)與口腔鱗癌進(jìn)展的關(guān)系。方法:利用SP免疫組化染色法,對前期研究的隨訪患者中隨機(jī)選取95名患者調(diào)取病理組織蠟塊,切片染色。結(jié)果判斷結(jié)合細(xì)胞計(jì)數(shù)法和光密度分析法。使用SPSS及Graph Pad等統(tǒng)計(jì)軟件用t檢驗(yàn)和Mann-Whitney秩和檢驗(yàn)及Kaplan-Meier生存分析法對數(shù)據(jù)進(jìn)行分析。結(jié)果:1.根據(jù)EHMT1的免疫組化染色結(jié)果,95例口腔鱗癌患者的組織切片染色平均光密度(Mean optical density,MOD)值在34.53~167.38之間。取中位數(shù)119.86。將患者分為兩組:EHMT1低表達(dá)組,即MOD值小于119.86的患者;EHMT1高表達(dá)組,即MOD值大于等于119.86的患者。采用Kaplan-Meier生存分析法用GraphPad6.0繪制生存曲線,并使用Log-rank法對所得出的數(shù)據(jù)進(jìn)行檢驗(yàn)。P=0.03850.05,結(jié)果表明EHMT1低表達(dá)組患者的生存率高于EHMT1高表達(dá)組,差異具有統(tǒng)計(jì)學(xué)意義。2.根據(jù)患者的腫瘤轉(zhuǎn)移情況將患者分為轉(zhuǎn)移組(metastasis)和非轉(zhuǎn)移組(non-metastasis),對兩組患者的EHMT1表達(dá)情況進(jìn)行分析,用t檢驗(yàn)驗(yàn)證兩組的MOD值是否存在差異。結(jié)果為:P=0.0070.05,這說明兩組患者的EHMT1表達(dá)存在顯著差異。3.根據(jù)第一部分研究中的臨床病理參數(shù)分組后得出不同參數(shù)的陽性率。運(yùn)用Mann-Whitney秩和檢驗(yàn)檢測各參數(shù)的統(tǒng)計(jì)學(xué)差異。結(jié)果顯示晚期口腔鱗癌患者的EHMT1表達(dá)與早期患者相比較存在統(tǒng)計(jì)學(xué)差異。P0.05小結(jié):1.EHMT1在口腔鱗癌中的表達(dá)對患者術(shù)后生存率存在影響,患者EHMT1表達(dá)水平與其術(shù)后生存時(shí)間呈負(fù)相關(guān)。2.EHMT1在口腔鱗癌中的表達(dá)對患者腫瘤轉(zhuǎn)移存在影響,患者EHMT1表達(dá)水平與其腫瘤轉(zhuǎn)移率呈正相關(guān)。3.晚期患者的EHMT1陽性率與早期患者相比存在顯著統(tǒng)計(jì)學(xué)差異,提示EHMT1的表達(dá)可能與腫瘤的進(jìn)展有關(guān)。第三部分:亞砷酸鈉抑制口腔鱗狀細(xì)胞癌增殖、促凋亡及機(jī)制研究目的:利用CCK8法、Annexin V/PI雙染法及Western blot等方法探討亞砷酸鈉調(diào)控Wnt信號通路對口腔鱗狀細(xì)胞癌增殖及凋亡的影響。方法:1.25、2.5、5、10、20μmol/L的亞砷酸鈉處理人口腔鱗狀細(xì)胞癌細(xì)胞株HN12,24、48、72h后,CCK8實(shí)驗(yàn)檢測細(xì)胞增殖;0、10μmol/L的亞砷酸鈉處理HN12細(xì)胞48h后,流式細(xì)胞儀檢測細(xì)胞凋亡,Western blot檢測Cleaved caspase3、β-catenin、Cyclin D1蛋白表達(dá);后續(xù)實(shí)驗(yàn)分為對照組、亞砷酸鈉組、激活劑+亞砷酸鈉組,各組細(xì)胞處理48h后,CCK8實(shí)驗(yàn)、流式細(xì)胞術(shù)及Western blot分別檢測三組細(xì)胞的增殖、凋亡及Cleaved caspase3、β-catenin、Cyclin D1蛋白表達(dá)。結(jié)果:1.隨著時(shí)間及濃度增加細(xì)胞抑制率均顯著升高,具有時(shí)間和濃度依賴性(P0.05或P0.01),根據(jù)IC50選擇10μmol/L的亞砷酸鈉作為后續(xù)研究;2.10μmol/L的亞砷酸鈉組細(xì)胞凋亡率及Cleaved caspase3蛋白表達(dá)顯著高于0μmol/L組,β-catenin、Cyclin D1蛋白表達(dá)顯著低于0μmol/L組(P0.01);3.亞砷酸鈉組及激活劑+亞砷酸鈉組細(xì)胞凋亡率、細(xì)胞抑制率及Cleaved caspase3蛋白表達(dá)均顯著高于對照組,β-catenin、Cyclin D1蛋白表達(dá)顯著低于對照組(P0.01);4.激活劑+亞砷酸鈉組細(xì)胞凋亡率、細(xì)胞抑制率及Cleaved caspase3蛋白表達(dá)均顯著低于亞砷酸鈉組,β-catenin、Cyclin D1蛋白表達(dá)顯著高于亞砷酸鈉組(P0.01)。小結(jié):1.研究證明亞砷酸鈉能夠抑制HN12細(xì)胞的增值同時(shí)促進(jìn)其凋亡。2.經(jīng)過亞砷酸鈉處理的HN12細(xì)胞其凋亡相關(guān)蛋白Cleaved caspase3表達(dá)升高,而Wnt信號通路相關(guān)的β-catenin、Cyclin D1蛋白表達(dá)降低。3.激活Wnt信號通路后亞砷酸鈉的促凋亡作用受到抑制。結(jié)論:1.河南地區(qū)口腔鱗癌的發(fā)病特點(diǎn)及患者術(shù)后的生存率和復(fù)發(fā)率與國內(nèi)發(fā)達(dá)地區(qū)相關(guān)報(bào)道情況大致相同。表明我省的口腔鱗癌的治療水平處于全國前列。2.EHMT1在口腔鱗癌中的異常表達(dá),特別是在轉(zhuǎn)移性患者癌組織中的高表達(dá)提示EHMT1可能成為口腔鱗癌轉(zhuǎn)移的生物標(biāo)志物。3.亞砷酸鈉可抑制口腔鱗狀細(xì)胞癌增殖及促進(jìn)凋亡,其機(jī)制與Wnt信號通路的調(diào)控有關(guān)。
[Abstract]:Background: oral squamous cell carcinoma (OSCC), also known as oral squamous cell carcinoma, is one of the most common malignant tumors occurring in the oral and maxillofacial region. Although the epidemiological investigation and retrospective study of oral squamous cell carcinoma are emerging at home and abroad, there are few related studies in Henan province. The study of the characteristics and survival rate of oral squamous cell carcinoma in Henan is helpful to improve the overall level of.Micro RNA (MI RNA) in oral squamous cell carcinoma (oral squamous cell carcinoma), which is a hot research direction for oral squamous cell carcinoma. It has been proved that MI RNA, a non coded small RNA, is the result of the targeting and specific action of M RNA or starting factor. The target RNA degrades or inhibits its translation and reduces the expression of related target gene proteins and plays an important role in physiological and pathological regulation. The current study has found that the abnormal expression of MI RNA is closely related to the disease, especially cancer. A key step in cancer progression is to proliferate out of control. Recent evidence shows that MI RNA is used as a RNA. The abnormal expression of tumor oncogene or tumor suppressor gene is a key factor affecting the growth of tumor cells. In the early gene chip study, we have found the high expression of MI RNA-602 in oral squamous cell carcinoma, and found that the EHMT1 (normal chromatin methyltransferase 1) gene can be transcribed by methylation histone Level inhibits the expression of MAL gene, while mi R-602 can further inhibit the MAL m RNA that has been transcribed. The EHMT1/mi R-602 transcript affects the stability of the MAL gene by synergistic effect at the transcriptional and post transcriptional levels, thus regulating the metastasis of oral squamous cell carcinoma. This study is intended to be used in EHMT1 in oral squamous cell carcinoma. The level of expression is explored to find reliable biomarkers for the metastasis of oral squamous cell carcinoma. The current standardized treatment for oral squamous cell carcinoma includes surgical resection and subsequent adjuvant radiotherapy and chemotherapy. Recent domestic and foreign studies have made some progress in the comprehensive treatment of oral squamous cell carcinoma, but the overall prognosis is still not. Tai Le Guan. The role of neoadjuvant chemotherapy (NACT) in the treatment of oral squamous cell carcinoma has become an important field of exploration. The new adjuvant chemotherapy refers to the systemic chemotherapy before the implementation of local treatment methods (such as surgery or radiotherapy). The purpose is to reduce the mass and to kill the invisible transfer cells as early as possible for the follow-up operation and radiotherapy for the treatment of [36-4. 9]. aims to reduce the range of surgical excision, improve local regional function, control and reduce distal metastasis, thereby reduce mortality and recurrence, and improve treatment results. However, the adaptation of neoadjuvant chemotherapy in oral cancer has not been clearly defined. Most studies have failed to show neoadjuvant chemotherapy in resectable oral squamous cell carcinoma. The control of regional lesions and the significant impact of the overall survival rate. In the study of some patients with advanced local lesions and non resectable oral squamous cell carcinoma, neoadjuvant chemotherapy can significantly control the growth of the tumor, narrow the range of the lesion and create an opportunity for surgical excision. Resectable oral squamous cell carcinoma, distal metastasis and resectability and prognostic function have some positive effects, but need to be further verified. Currently, chemotherapy is performed mainly through fluorouracil, cisplatin, adriamycin and other drugs. However, these drugs are susceptible to drug resistance while exerting anti-cancer effects. It is necessary to find a new effective antitumor drug to improve the patient's survival rate. Arsenic (mainly arsenite, Na As O2) has been studied more in the blood system tumor methods, in gastric cancer, lung cancer and other solid tumors, but the overall study is less, and the study of oral squamous cell carcinoma is not clear. Therefore, this study is examined. The effect of sodium arsenite on the proliferation and apoptosis of human oral squamous cell carcinoma HN12 cells in vitro and its mechanism are discussed in order to provide a theoretical basis for the clinical effect of sodium arsenite. Part 1: retrospective analysis of 461 cases of oral squamous cell carcinoma in Henan: through the First Affiliated Hospital of Zhengzhou University from 2007 to 2012 The case data of oral squamous cell carcinoma patients in oral and maxillofacial surgery were collected and arranged to summarize the characteristics of oral squamous cell carcinoma in Henan area. The factors related to the incidence of oral squamous cell carcinoma and the survival rate and recurrence rate were analyzed. The selection and recurrence prevention of oral squamous cell carcinoma in Henan area and the evaluation of the prognosis were evaluated. Methods: to collect and collate the medical records of oral squamous cell carcinoma patients in oral and maxillofacial surgery in the First Affiliated Hospital of Zhengzhou University from 2007 to 2012. The data of patients' cases were statistically analyzed with SPSS21.0, Graph Pad6.0 and other statistical software, and the age, sex, region, and tumor score of the patients were statistically analyzed. Degree, pathological TNM staging and other characteristics. The object of the study was the oral squamous cell carcinoma in Henan area, which was in accordance with the screening conditions. The recurrence rate analysis involved in the study was analyzed with chi square test. The selection of alpha =0.05 as a test level, when P0.05 considered a statistical significance. In the study of factors affecting the survival time after the operation, The survival curve was plotted by Kaplan-Meier survival analysis and the data obtained by Log-rank were tested. Results: the basic analysis of 461 cases of oral squamous cell carcinoma in 1 Henan areas was analyzed in 461 cases of oral squamous cell carcinoma in 280 men and 181 women; the age of onset was mainly at the age of 50-79; the patient was significantly higher than that of the 461 patients. The patients in his region, in addition to Sanmenxia, Jiyuan, Hebi and Luoyang in Northwest Henan were less distributed, compared with Zhoukou City, Kaifeng City and Shangqiu city in Eastern Henan Province, and the majority of patients with middle and high differentiation of oral squamous cell carcinoma were found in the patients. The recurrence rate and survival rate of the buccal mucosa and gingival incidence were three.2. in 95 cases of oral squamous cell carcinoma in Henan area. A follow-up study was conducted in 461 patients in the early study. The recurrence rate and survival rate of these patients were investigated, age, and the survival rate of the tumor. It was also observed that the degree of tumor differentiation and the clinical stage of the tumor had an impact on the recurrence rate; for patients in the late stage (IV phase), adjuvant chemotherapy had an effect on the survival rate of the patients; for patients with low differentiation, the adjuvant therapy of oral squamous cell carcinoma had an impact on the recurrence rate of the patients. Summary: 1 Henan The distribution of oral squamous cell carcinoma in Henan region shows that there are regional differences in the distribution of oral squamous cell carcinoma in the region. The reasons for this phenomenon may be mainly due to the difference of traffic conditions, the difference of medical conditions in local hospitals or primary hospitals. From the results of this study, the incidence of oral squamous cell carcinoma in Henan area is characterized and complete. The country is basically consistent. But at the age of onset, the number of patients at the age of 70-79 is also particularly prominent, and the specific factors that cause this result remain to be further studied. In these patients, the number of patients with lower degree of differentiation is less, which may be related to the inherent defects of the Broders/WHO histology classification system itself related to the impact of.2 on oral scales. The results of the related factors of recurrence rate after cancer show that age and sex have no effect on the recurrence rate of oral squamous cell carcinoma in the oral squamous cell cancer patients involved in the study. In the study, the pathological and clinical stages have an impact on the postoperative recurrence rate of oral squamous cell carcinoma. The postoperative recurrence rate also affects the postoperative survival rate of.3 in oral squamous cell carcinoma. It is found that the age and the clinical stage of the tumor may be the factors affecting the postoperative survival rate for the patients with oral squamous cell carcinoma. The survival time of the patients in the high age group is lower than the low age group, and the postoperative survival rate of the I patients is high. The study also found that chemotherapy is helpful to improve postoperative survival in patients with advanced (IV) oral squamous cell carcinoma, suggesting that adjuvant chemotherapy for advanced oral squamous cell carcinoma is still worth studying for advanced patients. Second: the second part: the expression of EHMT1 in oral squamous cell carcinoma: to understand EHM The expression of T1 in oral squamous cell carcinoma was used to explore the relationship between the expression of EHMT1 and the progress of oral squamous cell carcinoma. Methods: using SP immunohistochemical staining, 95 patients were randomly selected for pathological tissue wax block and stained. The results were combined with cell count and light density analysis. SPSS and Graph P were used. The data were analyzed by t test, Mann-Whitney rank test and Kaplan-Meier survival analysis. Results: 1. according to the immunohistochemical staining results of EHMT1, the mean optical density (Mean optical density, MOD) of 95 cases of oral squamous cell carcinoma was between 34.53~167.38. The median 119.86. was divided into the patients. The two group: EHMT1 low expression group, MOD value less than 119.86 patients; EHMT1 high expression group, that is, the MOD value is greater than 119.86. Using the Kaplan-Meier survival analysis method to use GraphPad6.0 to draw the survival curve, and use the Log-rank method to test the obtained data. The results show that the survival rate of the patients with low expression of EHMT1 is higher than EH. MT1 high expression group, the difference was statistically significant.2. was divided into the metastasis group (metastasis) and the non transfer group (non-metastasis) according to the tumor metastasis of the patients. The EHMT1 expression in the two groups was analyzed, and the t test was used to verify the difference in the MOD value of the two groups. The result was P=0.0070.05, which indicated the EHMT1 table of the two groups of patients. The positive rates of different parameters were obtained after grouping the clinicopathological parameters in the first part of the study. The statistical difference between the parameters were detected by the Mann-Whitney rank sum test. The results showed that the EHMT1 expression in the patients with advanced oral squamous cell carcinoma was compared with the early patients in a statistically significant difference of.P0.05: 1.EHMT1 at the mouth of the oral squamous cell carcinoma (1.EHMT1). The expression of EHMT1 in the squamous cell carcinoma has an effect on the postoperative survival rate. The expression level of the patient is negatively correlated with the survival time of the patients with the postoperative survival time. The expression of.2.EHMT1 in oral squamous cell carcinoma has an influence on the metastasis of the patients. The expression level of the patient's EHMT1 is positively related to the metastasis rate of the tumor, and the positive rate of EHMT1 in the late.3. patients is compared with the early patients. In the significant statistical difference, the expression of EHMT1 may be related to the progression of tumor. Third part: sodium arsenite inhibits the proliferation, apoptosis and mechanism of oral squamous cell carcinoma. CCK8, Annexin V/PI double staining and Western blot are used to investigate the proliferation and proliferation of Wnt signaling pathway by sodium arsenite to regulate the proliferation of oral squamous cell carcinoma. The effect of apoptosis. Methods: 1.25,2.5,5,10,20 mu mol/L sodium arsenite treated human oral squamous cell carcinoma cell line HN12,24,48,72h, and the cell proliferation was detected by CCK8 experiment. After HN12 cell 48h was treated with sodium arsenite of 0,10 mol/L, the apoptosis was detected by flow cytometry. Western blot was used to detect Cleaved Caspase3. The follow-up experiments were divided into control group, sodium arsenite group, activator and sodium arsenite group. After 48h, CCK8 experiment, flow cytometry and Western blot were used to detect the proliferation, apoptosis and the expression of Cleaved Caspase3, Cleaved Caspase3, -catenin and Cyclin D1 protein respectively. Results: 1. with time and concentration, the cell inhibition rate increased significantly, with the increase of cell inhibition rate. With time and concentration dependence (P0.05 or P0.01), sodium arsenite was selected according to IC50 as a follow-up study. The apoptosis rate and the expression of Cleaved Caspase3 protein in the 2.10 mol/L sodium arsenite group were significantly higher than that of the 0 mu mol/L group, and the expression of beta -catenin, Cyclin D1 protein was significantly lower than that of the 0 micron mol/L group; 3. sodium arsenite group and activator + subgroup + subgroup The apoptotic rate, cell inhibition rate and Cleaved Caspase3 protein expression in sodium arsenate group were significantly higher than those in control group, beta -catenin, Cyclin D1 eggs.
【學(xué)位授予單位】：鄭州大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R739.8

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