【摘要】：非小細(xì)胞肺癌無(wú)論在男女腫瘤中都具有較高的發(fā)病率和極高死亡率。近些年來(lái),男性肺癌患者的發(fā)病達(dá)到平臺(tái)期,女性肺癌發(fā)病率卻逐年上升。2014年全國(guó)腫瘤登記中心發(fā)布的數(shù)據(jù)顯示:我國(guó)2010年女性新增肺癌發(fā)病病例為18.96萬(wàn),居女性第2位惡性腫瘤,占女性新發(fā)惡性腫瘤的14.75%。女性肺癌出現(xiàn)年輕化、發(fā)病率高的不同特點(diǎn)。這類(lèi)女性肺癌大多無(wú)抽煙史,而且腺癌更多。雖然女性肺癌患者的發(fā)病增多,部分研究歸因于女性抽煙人群的增多、女性烹調(diào)油煙或被動(dòng)抽煙、女性對(duì)煙霧的易感性、人乳頭瘤病毒(HPV)感染或現(xiàn)代社會(huì)女性生活壓力增大造成的影響。但部分文獻(xiàn)研究卻得不到此種結(jié)論。不容忽視的是煙霧對(duì)肺癌影響是以鱗癌發(fā)病為主要表現(xiàn)的。以腺癌為主的女性肺癌增多和年輕化是很難解釋的。男女之間性別差異影響著非小細(xì)胞肺癌發(fā)生、疾病進(jìn)展和分子生物學(xué)不同特性,并決定治療效果和預(yù)后。男女之間最大區(qū)別為性激素不同。性激素中最主要激素是雌激素。雌激素(Estrogen)是一種甾體類(lèi)固醇性激素,人體中的雌激素有三種:雌二醇、雌三醇和雌酮。其中雌二醇活性最強(qiáng)。女性雌激素主要由卵巢的卵泡分泌,少量由女性懷孕后的胎盤(pán)產(chǎn)生,和雌激素受體具有高度的親和力。在絕經(jīng)后女性中,卵巢不再產(chǎn)生雌激素素,血清雌二醇水平顯著下降。研究表明雌激素在體內(nèi)或體外試驗(yàn)中都可誘導(dǎo)腫瘤細(xì)胞的增殖,抗雌激素藥物可以阻斷這種作用。其次是孕激素,孕激素也是女性甾體激素,由卵巢黃體產(chǎn)生的孕激素是孕酮。促黃體生成素(LH)是垂體前葉嗜堿性細(xì)胞分泌的一種糖蛋白激素,主要是促進(jìn)卵巢排卵,在FSH的協(xié)同作用下,形成黃體并分泌孕激素。促卵泡生成激素(FSH)是垂體前葉嗜堿性細(xì)胞分泌的一種糖蛋白激素,其主要功能是促進(jìn)卵巢的卵泡發(fā)育和成熟。由卵巢的黃體分泌,主要功能是促使子宮內(nèi)膜從增殖期轉(zhuǎn)變?yōu)榉置谄凇４萍に厥荏w(ER)和孕激素受體(PR)與乳腺癌和子宮內(nèi)膜癌相關(guān),在乳腺癌組織中雌、孕激素受體狀況是判斷乳腺癌和子宮內(nèi)膜癌預(yù)后及給予激素治療的重要依據(jù)。雌、孕激素受體的檢測(cè)用于指導(dǎo)乳腺癌的內(nèi)分泌治療,已在臨床上廣泛采用并取得了顯著的療效,改善了乳腺癌和子宮內(nèi)膜癌患者的預(yù)后。因此把乳腺癌等依賴(lài)性激素靶器官腫瘤稱(chēng)為性激素依賴(lài)性腫瘤。不僅如此,在非性激素靶器官的腫瘤組織中存在性激素受體,以往研究表明正常人及肺癌患者的肺組織中均存在性激素受體,肺癌組織中的性激素受體水平明顯高于正常人,提出肺癌也是性激素依賴(lài)性腫瘤。雌激素受體存在兩個(gè)亞型,為雌激素受體α(ERα)和雌激素受體β(ERβ)。在以往研究中ERα在肺癌中表達(dá)還存在爭(zhēng)議,但大部分認(rèn)為ERα在肺癌中表達(dá)不明顯,肺癌腫瘤中主要表達(dá)為ERβ。ERβ在肺癌的發(fā)生發(fā)展中具有重要作用,特別在以性別作為影響因素性激素依賴(lài)性腫瘤中具有重要影響。雌激素及其受體在腫瘤中作用機(jī)制可能為:雌激素進(jìn)入腫瘤細(xì)胞質(zhì)以后和特異性受體結(jié)合,形成激素受體復(fù)合物。激素受體復(fù)合物可以穿過(guò)核膜,進(jìn)入細(xì)胞核,和核內(nèi)受體結(jié)合并單體二聚化。從而影響細(xì)胞核中脫氧核糖核酸(DNA)的轉(zhuǎn)錄,合成了新的蛋白質(zhì),形成了新的腫瘤。雖然抗雌激素治療在體外實(shí)驗(yàn)或動(dòng)物實(shí)驗(yàn)中取得良好效果。但是,大部分女性肺癌患者給予抗性激素治療后,并沒(méi)有得到較好的療效和取得更長(zhǎng)的生存時(shí)間,這成為靶向抗雌激素治療不足。可能為性激素依賴(lài)型肺癌患者的判斷和篩選條件影響了此類(lèi)患者的治療。這樣,對(duì)性激素依賴(lài)型肺癌判斷和篩選條件成為首要研究方向。通過(guò)研究我們發(fā)現(xiàn)ERβ可能是性激素依賴(lài)性女性肺癌的一個(gè)重要因素。同時(shí)絕經(jīng)前雌激素升高和絕經(jīng)后孕激素的降低也可能是性激素依賴(lài)性肺癌的一個(gè)重要因素。通過(guò)合成針對(duì)ERβ的si RNA并構(gòu)建與之相應(yīng)的載體,對(duì)生長(zhǎng)期培養(yǎng)的ERβ高表達(dá)的的細(xì)胞株LTEP-a2進(jìn)行轉(zhuǎn)染,對(duì)比陰性對(duì)照組和空白對(duì)照組;RT-PCR檢測(cè)轉(zhuǎn)染細(xì)胞ERβm RNA的表達(dá),Western blot法檢測(cè)ERβ蛋白的表達(dá)。噻唑藍(lán)比色法(MTT法)檢測(cè)雌激素培養(yǎng)的轉(zhuǎn)染的細(xì)胞生長(zhǎng),流式細(xì)胞儀檢測(cè)培養(yǎng)的轉(zhuǎn)染的肺癌細(xì)胞的凋亡情況。在體外試驗(yàn)中佐證了ERβ可能是性激素依賴(lài)性肺癌的一個(gè)重要因素。通過(guò)抗性激素治療效果作為判斷女性性激素依賴(lài)性肺癌的依據(jù),探討其與一般情況及病理學(xué)因素之間的相互關(guān)系,篩選女性非小細(xì)胞肺癌性激素依賴(lài)性患者的影響因素。單因素分析篩選出與女性性激素依賴(lài)性肺癌相關(guān)因素,Logistic回歸分析進(jìn)一步篩選判斷。肺癌發(fā)生發(fā)展是一個(gè)復(fù)雜的過(guò)程,性激素依賴(lài)性女性肺癌提出也是一個(gè)新的課題。針對(duì)性激素和相關(guān)受體及其相關(guān)機(jī)制的研究,有助于實(shí)現(xiàn)肺癌個(gè)性化診斷和治療。本研究嘗試從不同方面尋找此類(lèi)患者的篩選條件,為女性非小細(xì)胞肺癌提供一種新的治療方法。本研究包括以下四個(gè)部分章節(jié)第一部分:女性非小細(xì)胞肺癌患者雌激素受體的表達(dá)及其臨床意義目的:檢測(cè)女性非小細(xì)胞肺癌患者雌激素受體表達(dá),研究其與病理學(xué)因素及術(shù)后生存率的關(guān)系,探討女性非小細(xì)胞肺癌患者雌激素受體表達(dá)的臨床檢測(cè)價(jià)值。方法:應(yīng)用免疫組化法檢測(cè)2007年3月至2012年05月江門(mén)市中心醫(yī)院手術(shù)的125例女性非小細(xì)胞肺癌患者腫瘤標(biāo)本中雌激素受體ERα和ERβ,孕激素受體A(PRA)和孕激素受體(PRB)表達(dá),分析其影響因素。Kaplan-Meier生存曲線(xiàn)比較生存率。結(jié)果:1.125例非小胞肺癌患者ERα陽(yáng)性0例,所有肺癌腫瘤細(xì)胞未發(fā)現(xiàn)ERα陽(yáng)性。125例非小胞肺癌患者ERβ陽(yáng)性58例,陽(yáng)性率為46.4%。2.125例非小胞肺癌患者PRA陽(yáng)性0例,PRB陽(yáng)性0例,所有肺癌腫瘤細(xì)胞未發(fā)現(xiàn)PRA陽(yáng)性和PRB陽(yáng)性。3.ERβ陽(yáng)性表達(dá)與年齡大小、絕經(jīng)前后狀態(tài)、肺癌的病理類(lèi)型、分期有關(guān),其中腺癌的陽(yáng)性率最高,鱗癌的陽(yáng)性率最低。隨著分期增高,ERβ陽(yáng)性表達(dá)也越高(P0.05)。ERβ陽(yáng)性表達(dá)與腫瘤大小、分化程度、有無(wú)吸煙史無(wú)顯著差異(P0.05)。4.絕經(jīng)前ERβ陰性患者生存率明顯高于絕經(jīng)前ERβ陽(yáng)性女性非小細(xì)胞癌(P0.05);絕經(jīng)后ER?陽(yáng)性生存率明顯高于絕經(jīng)后女性非小細(xì)胞肺癌(P0.05)。結(jié)論:1.檢測(cè)女性非小細(xì)胞肺癌患者雌激素受體表達(dá)具有重要意義,可以有助于了解女性患者的術(shù)后生存情況,給此類(lèi)患者術(shù)后綜合治療提供綜合判斷。2.腫瘤組織雌激素受體ERβ水平可以影響女性非小細(xì)胞肺癌生長(zhǎng)和術(shù)后生存,可能是女性性激素依賴(lài)性非小細(xì)胞肺癌篩選的一個(gè)重要因素。第二部分:女性非小細(xì)胞肺癌患者外周血性激素水平與癌組織雌激素受體表達(dá)的關(guān)系目的:女性非小細(xì)胞肺癌患者呈現(xiàn)增多和年輕化的趨勢(shì),研究表明肺癌也為性激素依賴(lài)性腫瘤,性激素在女性非小細(xì)胞肺癌發(fā)生發(fā)展中具有重要影響。研究女性非小細(xì)胞肺癌患者癌組織中雌激素受體β表達(dá)與外周血性激素水平,探討其相關(guān)性及其臨床意義。方法:應(yīng)用磁性微粒分離的免疫酶聯(lián)分析檢測(cè)2006年3月至2012年05月中山大學(xué)附屬江門(mén)醫(yī)院手術(shù)的94例絕經(jīng)前和128例絕經(jīng)后女性非小細(xì)胞肺癌患者外周血性激素雌二醇(E2),卵泡生成激素(FSH),黃體生成激素(LH),孕酮(P)水平,術(shù)后免疫組化法檢測(cè)腫瘤標(biāo)本中雌激素受體ERβ表達(dá),分析其相互關(guān)系。結(jié)果:1.絕經(jīng)前94例女性非小細(xì)胞肺癌患者ERβ表達(dá)陽(yáng)性為36例,陽(yáng)性率為38.29%;絕經(jīng)后128例女性非小細(xì)胞肺癌患者ERβ表達(dá)陽(yáng)性為47例,陽(yáng)性率為36.72%。2所有女性患者孕激素受體PRA和PRB均為陰性,陽(yáng)性率為0。3.絕經(jīng)前女性非小細(xì)胞肺癌患者血清E2正常組中79例患者54例ERβ無(wú)明顯表達(dá),25例等級(jí)表達(dá);升高組中15例患者4例ERβ無(wú)明顯表達(dá),11例等級(jí)表達(dá)。絕經(jīng)前女性非小細(xì)胞肺癌患者血清E2正常組和升高組之間雌激素受體β表達(dá)有統(tǒng)計(jì)學(xué)意義(p0.05)。4.絕經(jīng)前女性非小細(xì)胞肺癌患者血清FSH、LH正常組和升高組雌激素受體表達(dá)無(wú)差異。血清P正常組和降低組雌激素受體表達(dá)無(wú)差異(p0.05)。5.絕經(jīng)后女性非小細(xì)胞肺癌患者血清P正常組中107例患者75例ERβ無(wú)明顯表達(dá),32例等級(jí)表達(dá);降低組中21例患者6例ERβ無(wú)明顯表達(dá),15例等級(jí)表達(dá)。絕經(jīng)后女性非小細(xì)胞肺癌患者血清P正常組和降低組雌激素受體表達(dá)有統(tǒng)計(jì)學(xué)意義(p0.05)。6絕經(jīng)后女性非小細(xì)胞肺癌患者血清E2、FSH、LH正常組和升高組雌激素受體表達(dá)無(wú)差異。(p0.05)。結(jié)論:1.女性非小細(xì)胞肺癌患者外周血存在性激素代謝的紊亂和失衡。2.絕經(jīng)前雌激素異�？赡苡绊懘萍に厥荏w表達(dá),絕經(jīng)后孕激素異�？赡苡绊懘萍に厥荏w表達(dá)。3.無(wú)論絕經(jīng)前期還是后期,LH和FSH激素的變化和腫瘤內(nèi)雌激素受體表達(dá)無(wú)差異。4.絕經(jīng)前血清中雌激素升高影響和絕經(jīng)后孕激素降低都可以影響雌激素受體表達(dá),可能為性激素依賴(lài)性肺癌的一個(gè)影響因素。第三部分:女性性激素依賴(lài)性肺癌的篩選因素目的:通過(guò)抗性激素治療效果作為判斷女性性激素依賴(lài)性肺癌的依據(jù),探討其與患者一般情況及病理學(xué)因素之間的相互關(guān)系,篩選女性非小細(xì)胞肺癌性激素依賴(lài)性患者的影響因素。方法:2007年8月至2014年8月中山大學(xué)附屬江門(mén)醫(yī)院治療的女性非小細(xì)胞肺癌患者,腫瘤進(jìn)展后給予他昔莫芬治療,如果有效判定為性激素依賴(lài)性肺癌入A組(29例);進(jìn)展后給予他昔莫芬治療無(wú)效或加重,判定為腫瘤非依賴(lài)性肺癌入B組(83例),單因素分析篩選出與女性性激素依賴(lài)性肺癌相關(guān)因素后,Logistic回歸分析進(jìn)一步篩選判斷。結(jié)果:女性性激依賴(lài)性肺癌與患者年齡、腫瘤分化程度、經(jīng)期時(shí)間、吸煙狀況、初潮年齡、月經(jīng)周期差異無(wú)統(tǒng)計(jì)學(xué)意義(p0.05),腫瘤類(lèi)型、婚姻狀況、雌激素受體表達(dá)、是否絕經(jīng)、生產(chǎn)次數(shù)與女性性激依賴(lài)性肺癌差異有統(tǒng)計(jì)學(xué)意義(p0.05)。采用多因素Logistic回歸模型分析,結(jié)果示腫瘤類(lèi)型、婚姻狀況、雌激素受體表達(dá)、是否絕經(jīng)、生產(chǎn)次數(shù)與女性性激依賴(lài)性肺癌差異有統(tǒng)計(jì)學(xué)意義(P0.05)。結(jié)論:腫瘤類(lèi)型特別是腺癌、婚姻狀況、雌激素受體β表達(dá)、是否絕經(jīng)、生產(chǎn)次數(shù)可能是女性性激素依賴(lài)性肺癌的篩選因素。第四部分:si RNA介導(dǎo)ERβ基因沉默對(duì)ERβ高表達(dá)的LTEP-a2細(xì)胞凋亡的影響目的:研究si RNA(Small Interference RNA)介導(dǎo)ERβ基因沉默對(duì)ERβ高表達(dá)的的LTEP-a2培養(yǎng)細(xì)胞凋亡作用及其對(duì)17-β雌二醇敏感性。方法:合成針對(duì)ERβ的si RNA,對(duì)生長(zhǎng)期培養(yǎng)的ERβ高表達(dá)的的LTEP-a2細(xì)胞進(jìn)行轉(zhuǎn)染,對(duì)比陰性對(duì)照組和空白對(duì)照組;RT-PCR檢測(cè)ERβm RNA的表達(dá),Western blot法檢測(cè)ERβ蛋白的表達(dá)。噻唑藍(lán)比色法(MTT法)檢測(cè)17-β雌二醇培養(yǎng)的轉(zhuǎn)染細(xì)胞的存活情況,確定IC50,流式細(xì)胞儀檢測(cè)培養(yǎng)的轉(zhuǎn)染的肺癌細(xì)胞的凋亡。結(jié)果:1.轉(zhuǎn)染si RNA組ERβm RNA表達(dá)明顯低于陰性對(duì)照組及空白對(duì)照組(PO.05)。陰性對(duì)照組及空白對(duì)照組比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)。2.轉(zhuǎn)染si RNA組ERβ蛋白表達(dá)低于陰性對(duì)照組及空白對(duì)照組(PO.05)。陰性對(duì)照組和空白對(duì)照組比較差異無(wú)統(tǒng)計(jì)學(xué)意義(P0.05)3.噻唑藍(lán)比色法(MTT法)結(jié)果表明不同濃度的17-β雌二醇干預(yù)后,ERβ-si RNA轉(zhuǎn)染組細(xì)胞與陰性對(duì)照組及空白對(duì)照組相比存活率出現(xiàn)顯著下降。(PO.05),雌二醇干預(yù)對(duì)LTEP-a2細(xì)胞生長(zhǎng)與陰性對(duì)照組及空白對(duì)照組相比,轉(zhuǎn)染組生長(zhǎng)明顯抑制(PO.05)4.轉(zhuǎn)染si RNA組在雌二醇干預(yù)后LTEP-a2細(xì)胞的凋亡率顯著增加,轉(zhuǎn)染組與陰性對(duì)照組與空白對(duì)照組比較,差異有顯著性(35.68±1.58%,3.55±0.33%,2.34±0.58%,PO.05)。結(jié)論:1.si RNA介導(dǎo)的ERβ基因沉默可以抑制雌激素藥物干預(yù)后肺癌細(xì)胞的增殖。2.si RNA介導(dǎo)的ERβ基因沉默可以增加雌激素藥物干預(yù)后肺癌細(xì)胞的凋亡。3.ERβ-si RNA可能為性激素依賴(lài)型肺癌治療的新的靶點(diǎn)。4.ERβ可能在篩選女性性激素依賴(lài)型肺癌非小細(xì)胞肺癌中發(fā)揮重要作用并且對(duì)這些肺癌加以鑒定,為此類(lèi)肺癌綜合治療提供幫助。
[Abstract]:Non small cell lung cancer has high incidence and high mortality in both male and female tumors. In recent years, the incidence of male lung cancer patients reached a platform stage. The incidence of female lung cancer increased year by year in.2014 year national tumor registration center, which showed that 189 thousand and 600 of the new cases of lung cancer in China in 2010 were women. Second of the second malignant tumors, which account for women's new malignant tumors, are young and have a high incidence. Most of these women have no history of smoking and more adenocarcinoma. Although the incidence of lung cancer in women is increased, some of the studies are due to the increase in female smokers, female cooking fumes or passive smoking, women. The susceptibility to smog, the infection of human papillomavirus (HPV), or the increasing pressure on the life of women in modern society. However, some literature studies have not been found. It is not to be ignored that the effects of smoke on lung cancer are mainly manifested in squamous cell carcinoma. The increase and younger of female lung cancer based on adenocarcinoma is difficult to explain. Gender differences affect the occurrence of non small cell lung cancer, disease progression and different molecular biology, and determine the therapeutic effect and prognosis. The biggest difference between men and women is sex hormone. The most important hormone in sex hormone is estrogen. Estrogen (Estrogen) is a steroid steroid hormone, and there are three kinds of estrogen in human body: Female Estradiol, estradiol and estrone. Female estradiol is the most active. Female estrogen is mainly secreted by ovarian follicles, a small amount is produced by the placenta after pregnancy and has a high affinity with estrogen receptor. In postmenopausal women, the ovaries no longer produce estrogen, and the level of serum estradiol drops significantly. The study shows that estrogen is in body. The proliferation of tumor cells can be induced in both internal and external tests. Progesterone is followed by progestin, progestin is also a female steroid hormone, progestin produced by the corpus luteum of the ovary is progesterone. LH is a glycoprotein hormone secreted by the basophilic cell of the anterior pituitary, mainly promoting the ovary. Ovulation, under the synergistic effect of FSH, forms the corpus luteum and secretes progesterone. Follicle stimulating hormone (FSH) is a glycoprotein hormone secreted by the basophil of the anterior pituitary. Its main function is to promote ovarian follicle development and maturation. The main function of the ovary is to induce the endometrium to change from the proliferating stage to the secretory phase. Hormone receptor (ER) and progesterone receptor (PR) are associated with breast cancer and endometrial cancer. The status of estrogen and progesterone receptor in breast cancer is an important basis for judging the prognosis of breast cancer and endometrial cancer and giving hormone therapy. A significant effect has been achieved to improve the prognosis of breast and endometrial cancer patients. Therefore, it is known as sex hormone dependent tumor for breast cancer and other dependent hormone target organs. Not only that, there is sex hormone receptor in the tumor tissues of the non sex hormone target organs. Previous studies have shown that the lung tissues of normal and lung cancer patients are all stored in the lung tissue. In sex hormone receptors, the level of sex hormone receptors in lung cancer tissues is significantly higher than that of normal people. Lung cancer is also a sex hormone dependent tumor. There are two subtypes of estrogen receptors, estrogen receptor alpha (ER alpha) and estrogen receptor beta (ER beta). In the previous study, the expression of ER alpha in lung cancer is still controversial, but most of them think that ER alpha is in lung cancer. The main expression of ER beta.ER beta in lung cancer plays an important role in the development of lung cancer, especially in sex as a factor dependent hormone dependent tumor. The mechanism of estrogen and its receptor in tumor may be after the entry of estrogen to the tumor cytoplasm and specific receptor junction. Corticosteroid receptor complex. Hormone receptor complex can pass through the nuclear membrane, enter the nucleus, combine with the receptor in the nucleus and dimerization. It affects the transcription of the nuclear DNA (DNA) in the nucleus, syntheses the new protein, and forms a new tumor. Although anti estrogen therapy has achieved good in vitro or in animal experiments. Good results. However, most of the women with lung cancer are given resistant hormone therapy, and they do not have a better effect and longer survival time. This becomes a lack of targeted anti estrogen therapy. It may be the diagnosis and screening of patients with sex hormone dependent lung cancer that affect the treatment of this type of patients. ER beta may be an important factor in sexual hormone dependent lung cancer. The increase of estrogen before menopause and the decrease of progesterone after menopause may also be an important factor in sex hormone dependent lung cancer. The construction and construction of Si RNA for ER beta may be an important factor in the development of lung cancer. Corresponding vector, transfection of ER beta highly expressed cell line LTEP-a2 in growth period, contrast negative control group and blank control group; RT-PCR detection of ER beta m RNA expression, Western blot method to detect the expression of ER beta protein. Thiazolazole colorimetric assay (MTT method) for detecting the growth of cells transfected by estrogen culture, flow cytometry The apoptosis of the transfected lung cancer cells was detected. In the test in vitro, it was confirmed that ER beta may be an important factor in sex hormone dependent lung cancer. Factors affecting sex hormone dependent patients with small cell lung cancer. Single factor analysis screened the factors associated with sex hormone dependent lung cancer in women. Logistic regression analysis was used to further screen and judge. The development of lung cancer is a complex process. Sex hormone dependent female lung cancer is also a new topic. The study of body and its related mechanisms helps to realize individualized diagnosis and treatment of lung cancer. This study attempts to find the screening conditions for such patients from different aspects and provide a new treatment for non small cell lung cancer in women. This study includes the following four chapters: the estrogen receptor of women with non-small cell lung cancer. Expression and clinical significance Objective: to detect the expression of estrogen receptor in female non-small cell lung cancer patients, to study the relationship with pathological factors and postoperative survival rate, and to explore the clinical value of estrogen receptor expression in female non-small cell lung cancer patients. Methods: the use of immunohistochemical method was used to detect the city center of Jiangmen from March 2007 to 05 months of 2012. The expression of estrogen receptor ER alpha and ER beta, progesterone receptor A (PRA) and progesterone receptor (PRB) in the tumor specimens of 125 patients with non-small cell lung cancer operated by hospital operation, and the comparison of the survival rate of the influencing factors.Kaplan-Meier survival curve. Results: 0 cases of non small cell lung cancer patients were positive for ER alpha, and all tumor cells of lung cancer did not find ER alpha Yang. There were 58 cases of ER beta positive in non small cell lung cancer patients in sex.125. The positive rate was PRA positive in 46.4%.2.125 cases of non small cell lung cancer and 0 cases of PRB positive. All lung cancer cells did not find PRA positive and PRB positive.3.ER beta positive expression and age size, premenopausal status, pathological type of lung cancer and staging, among which the positive rate of adenocarcinoma was the highest, scales were the highest, scales were the highest, scales were the highest, scales of squamous cell carcinoma. The positive rate of cancer was the lowest. The positive expression of ER beta was higher (P0.05), the positive expression of.ER beta and tumor size, the degree of differentiation, and the non smoking history had no significant difference (P0.05) the survival rate of ER beta negative patients before menopause was significantly higher than that of pre menopause ER beta positive female non small cell carcinoma (P0.05), and the positive rate of ER? Positive after menopause was significantly higher than that of menopause. Post female non small cell lung cancer (P0.05). Conclusion: 1. it is important to detect the expression of estrogen receptor in female non small cell lung cancer patients. It can help to understand the postoperative survival of female patients and provide comprehensive treatment for postoperative comprehensive treatment of the patients with.2. tumor tissue, the level of estrogen receptor ER beta can affect the non small cell lung of women. Cancer growth and postoperative survival may be an important factor in the screening of female sex hormone dependent non-small cell lung cancer. The second part: the relationship between the levels of peripheral blood hormone and the expression of estrogen receptor in cancerous tissues in women with non-small cell lung cancer: the trend of increasing and young growth in female non-small cell lung cancer patients, and the study of lung Cancer is also a sex hormone dependent tumor, and sex hormone plays an important role in the development of female non-small cell lung cancer. The study of estrogen receptor beta expression and peripheral blood hormone levels in the cancer tissues of women with non-small cell lung cancer and its clinical significance. Methods: immunoenzyme immunoassay for detection of 2 From March 006 to 05 months, 94 cases of premenopausal and 128 postmenopausal women with non small cell lung cancer were operated in the Jiangmen hospital, Zhongshan University, and 128 cases of postmenopausal women with non small cell lung cancer were peripheral blood hormone estradiol (E2), follicular hormone (FSH), luteinizing hormone (LH), progesterone (P) level. The expression of estrogen receptor ER beta in tumor specimens was detected by immunization after operation. Results: 1. the positive rate of ER beta expression in 94 non small cell lung cancer patients before menopause was 36, the positive rate was 38.29%, and the positive rate of ER beta expression was 47 in 128 cases of non small cell lung cancer patients after menopause, the positive rate of all female patients with 36.72%.2 was negative for progesterone receptor PRA and PRB, the positive rate was 0.3. premenopausal women non small cells. There was no obvious expression of ER beta in 79 patients with normal serum E2 in patients with lung cancer, 25 cases of grade expression, 4 cases of ER beta in 15 patients in the elevated group and 11 cases of grade expression. The expression of estrogen receptor beta between the normal group of E2 and the elevated group in pre menopausal women with non-small cell lung cancer was statistically significant (P0.05).4. premenopausal women were not small There was no difference in the expression of estrogen receptor in serum FSH, LH normal group and elevated group in the patients with cell lung cancer. There was no difference in the expression of estrogen receptor in the normal group of serum P and the lower group (P0.05). There were no obvious expression of ER beta in 75 cases of the normal group of non small cell lung cancer of postmenopausal women with non small cell lung cancer, 32 cases of ER beta, and 6 cases of ER beta in the 21 patients in the lower group. The expression of estrogen receptor in P normal group and lower group of non small cell lung cancer patients in postmenopausal women with non small cell lung cancer was statistically significant (P0.05).6 postmenopausal women with non small cell lung cancer serum E2, FSH, LH normal group and elevated group of estrogen receptor expression were not different. (P0.05). Conclusion: 1. female non small cell lung cancer patients (P0.05). (P0.05). (P0.05). Conclusion: Patients with non small cell lung cancer (P0.05). (P0.05). (P0.05). Conclusion: Patients with non small cell lung cancer (P0.05). (P0.05). (P0.05). Conclusion: the patients with non small cell lung cancer (P0.05). The disorder and imbalance of sex hormone metabolism in peripheral blood.2. premenopausal estrogen may affect the expression of estrogen receptor. Postmenopausal hormone abnormal progestin may affect the expression of estrogen receptor.3. in premenopausal or late menopause, the changes of LH and FSH hormones and there is no difference in the expression of estrogen receptor in the tumor.4. before menopause. Both high influence and postmenopausal progesterone decrease can affect the expression of estrogen receptor and may be an influential factor in sex hormone dependent lung cancer. The third part: screening factors for sex hormone dependent lung cancer in women: the basis for judging female sex induced lung cancer by the effect of resistant hormone therapy, and discuss it with the patients. The relationship between the pathological and pathological factors and the screening of factors affecting sex hormone dependent patients with non small cell lung cancer. Methods: from August 2007 to August 2014, women with non small cell lung cancer, affiliated to the Jiangmen hospital in Zhongshan University, were treated with celecoxifen after the tumor was progressed, if the sex hormone dependence was effectively judged. Lung cancer was admitted into group A (29 cases); the treatment was ineffective or aggravated after the treatment, and it was judged to be a tumor non dependent lung cancer in group B (83 cases). Single factor analysis screened the factors associated with sex hormone dependent lung cancer. Logistic regression analysis was used to further screen and judge. Results: female sex induced lung cancer and patient age, tumor differentiation process There was no significant difference in duration, duration of smoking, smoking status, menarche age and menstrual cycle (P0.05), tumor type, marital status, and estrogen intake.
【學(xué)位授予單位】：暨南大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2017
【分類(lèi)號(hào)】：R734.2

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