本文選題：非小細(xì)胞肺癌+GSTP1�。粎⒖迹�《南華大學(xué)》2015年碩士論文

【摘要】：目的肺癌是全球發(fā)病率和死亡率最高的惡性腫瘤之一,吉西他濱聯(lián)合鉑類是目前治療晚期非小細(xì)胞肺癌的標(biāo)準(zhǔn)方案之一。近代藥理遺傳學(xué)和基因組學(xué)研究表明,細(xì)胞基因的多樣性導(dǎo)致腫瘤細(xì)胞的異質(zhì)性。編碼基因的單核苷酸多態(tài)性與治療療效、不良反應(yīng)及預(yù)后有顯著相關(guān)性。本課題結(jié)合回顧性研究及臨床隨訪資料,旨在探討GSTP1和RRM1的基因多態(tài)性在晚期NSCLC中與GP方案化療敏感性的相關(guān)性,進一步篩選NSCLC有針對性以及可預(yù)見性的化療敏感預(yù)測因子,從而對NSCLC的臨床個體化化療提供分子生物學(xué)依據(jù)。方法收集2011-2013年我院老干內(nèi)科初次就診且經(jīng)病理組織學(xué)確診的晚期NSCLC患者52例,所有病例首次化療前抽血提取白細(xì)胞DNA,應(yīng)用Sanger測序法(雙脫氧鏈終止法)檢測GSTP1(I105V,A→G)及RRM1(C-37A、T-524C)位點基因多態(tài)性。所有52例患者均接受2-4周期GP方案化療,依據(jù)化療評定標(biāo)準(zhǔn)將52例患者分為化療敏感組和非敏感組。根據(jù)隨訪研究,分析GSTP1、RRM1基因多態(tài)性與GP方案化療敏感性(近期療效、遠(yuǎn)期療效)的相關(guān)性。結(jié)果1.GSTP1(I105V)基因有三種基因型:AA(61.5%)、GA(34.6%)、GG(3.8%);RRM1(C-37A)等位基因有三種基因型:CC(50.0%)、CA(38.5%)、AA(11.5%),RRM1(T-524C)等位基因有三種基因型:TT(46.2%)、TC(38.5%)、CC(15.4%);RRM1兩個位點(T-524C、C-37A)依排列組合存在9種基因型分型,其頻率分別為:AA/CC(5.8%)、AA/TC(5.8%)、CA/CC(5.8%)、CA/TC(32.7%)、CC/TT(46.2%)、CC/CC(3.8%)、AA/TT(0%)、CA/TT(0%)、CC/TC(0%),AA/TT、CA/TT、CC/TC這3種基因型未檢出。2.GSTP1(I105V)位點各基因型與近期療效無明顯相關(guān)性(P0.05);RRM1(C-37A)位點CA基因型近期緩解率明顯高于AA及CC基因型(P0.05);RRM1(T-524C)位點TC基因型近期緩解率明顯高于TT及CC基因型(P0.05);RRM1(T-524C、C-37A)兩個位點CA/TC基因型近期緩解率明顯高于除CA/TC外所有其它基因型(P0.05)(具體基因型為AA/CC、AA/TC、CA/CC、CC/TT、CC/CC)。3.調(diào)整了年齡、性別、病理類型、臨床分期后,CA/TC基因型近期緩解率是除CA/TC外所有其它基因型的7.14倍(P=0.008)。4.高齡、分期較晚和基因型均與PFS密切相關(guān)(P0.05),低齡、分期較早和近期療效較高均與OS密切相關(guān)(P0.05)。GSTP1(I105V)位點AA基因型疾病進展風(fēng)險是AG及GG基因型的1.266倍(P0.05),RRM1(T-524C、C-37A)位點除CA/TC外所有其它基因型疾病進展風(fēng)險是CA/TC基因型的2.598倍(P0.05)。5.GSTP1(I105V)位點AG及GG基因型中位PFS高于AA基因型(9.9月vs.7.7月,P=0.046);RRM1(T-524C、C-37A)位點CA/TC基因型中位PFS高于除CA/TC外所有其它基因型患者(13.7月vs.7.4月,P=0.000)。結(jié)論1.GSTP1(I105V)、RRM1(T-524C、C-37A)與晚期NSCLC患者對GP方案化療的敏感性有關(guān);2.GSTP1(I105V)位點AG及GG基因型與RRM1(T-524C、C-37A)位點CA/TC基因型的PFS更長。3.GSTP1(I105V)、RRM1(T-524C、C-37A)與OS無明顯相關(guān)性。
[Abstract]:Objective lung cancer is one of malignant tumors with the highest morbidity and mortality worldwide, gemcitabine combined with platinum is one of the standard solution in the treatment of advanced non-small cell lung cancer. Modern pharmacological studies show that genetics and genomics, gene diversity of cells leads to the heterogeneity of tumor cells. Single nucleotide polymorphism and therapeutic effect of the gene encoding significantly the correlation of adverse reaction and prognosis. This paper reviews research and clinical follow-up, aims to explore the correlation between gene polymorphism and RRM1 GSTP1 in advanced NSCLC and GP chemotherapy sensitivity, further screening of NSCLC targeted and predictable chemotherapy sensitive predictors of NSCLC, so as to provide clinical individual chemotherapy molecules biological basis. Methods 2011-2013 years in our hospital for medical first visit and confirmed by pathology in 52 patients with advanced NSCLC 渚，

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