本文選題：非小細(xì)胞肺癌　切入點(diǎn)：TYMS　出處：《南華大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：目的本文探討了人胸苷酸合成酶(TYMS)和谷胱甘肽S轉(zhuǎn)移酶P1(GSTP1)基因多態(tài)性與晚期非小細(xì)胞肺癌患者(NSCLC)對培美曲塞聯(lián)合鉑類方案(PP/PC方案)化療敏感性的關(guān)系。為進(jìn)一步研究培美曲塞聯(lián)合鉑類藥物方案對NSCLC化療敏感性指標(biāo)及個體化治療提供參考。方法在2013年1月1日-2015年1月1日的時間段內(nèi),收集并篩選出晚期NSCLC腺癌病例30例,所有病例首次化療前抽取靜脈血2m1,提取全血基因組DNA,應(yīng)用實(shí)時焦磷酸測序技術(shù)檢測TYMS、GSTP1基因多態(tài)性,對患者基因型進(jìn)行分組。采用隨訪研究,探討TYMS、GSTP1基因多態(tài)性與PP/PC方案敏感性(近期療效、遠(yuǎn)期療效)之間的關(guān)系。結(jié)果1.基因型檢測結(jié)果:在研究病例中,GSTP1基因第105位氨基酸位點(diǎn)存在3種基因型,基因型分布頻率分別為A/A(60%),A/G(36.3%)和G/G(3.3%)。TYMS基因根據(jù)5`UTR區(qū)存在的28bp串聯(lián)重復(fù)次數(shù)分3型:2R/2R(3.3%)、2R/3R(43.4%)、3R/3R(53.3%)。2.免疫組化病例14例,其中TS蛋白陽性表達(dá)9例(64.3%),TS蛋白陰性表達(dá)5例(35.7%)。2R/2R、2R/3R為低表達(dá)組,3R/3R型為高表達(dá)組,TYMS 2R/3R基因型和TS蛋白表達(dá)存在負(fù)相關(guān)性(γ=0.757,P=0.036)。3.在單因素分析中,GSTP1(I105V)位點(diǎn)攜帶G等位基因的患者近期有效率(58.3%)顯著高于A/A基因型患者(16.7%)(P0.05),攜帶G等位基因患者的中位PFS長于A/A基因型(5.7月vs.4.0月,P=0.047)。另外患者的年齡、分化程度、臨床分期,近期療效和PFS相關(guān)性比較無統(tǒng)計學(xué)差異。4.在單因素分析中,TYMS基因型與近期有效率相關(guān)性無統(tǒng)計學(xué)差異(P0.05),與患者PFS相關(guān)性有差異,TYMS基因型為3R/3R的患者中位PFS小于2R/3R基因型的患者(4.3月vs7.8月,P=0.036),5.COX比例風(fēng)險模型多因素分析性別、基因型與PFS之間的相關(guān)性,性別和基因型都與PFS相關(guān),其中女性的疾病進(jìn)展風(fēng)險是男性的2.12倍(P0.05),GSTP1(I105V)基因型為A/A的患者疾病進(jìn)展風(fēng)險是攜帶G等位基因患者的1.537倍(P0.05),TYMS基因型為3R/3R的患者疾病進(jìn)展風(fēng)險是2R/3R基因型患者的1.763倍(P0.05)。結(jié)論:1.晚期NSCLC患者PP/PC方案中,GSTP1(I105V)位點(diǎn)攜帶G等位基因的患者的近期療效和PFS均高于A/A型患者;TYMS基因5`UTR區(qū)基因型為2R/3R型的患者PFS長于3R/3R型患者,更具有生存期優(yōu)勢。2.GSTP1(I105V)和TYMS 2R/3R基因型多態(tài)性檢測結(jié)果可作為預(yù)測晚期非小細(xì)胞肺腺癌患者培美曲塞聯(lián)合鉑類藥物方案選擇的參考指標(biāo)之一。3.晚期NSCLC患者外周血白細(xì)胞的TYMS(2R/3R)基因型可能反映了腫瘤細(xì)胞內(nèi)TYMS酶的含量。
[Abstract]:Objective to investigate the relationship between the polymorphism of human thymidine synthase (TYMS) and glutathione S-transferase (GSTP1) gene and the chemosensitivity of advanced non-small cell lung cancer (NSCLC) to pemetrexide combined with PPP / PC regimen. To study the chemosensitivity and individualized treatment of NSCLC with pemetrexide combined with platinum regimen. Methods during the period from January 1st 2013 to January 1st 2015, 30 cases of advanced NSCLC adenocarcinoma were collected and screened. Venous blood 2ml was extracted from all patients before the first chemotherapy. The genomic DNA was extracted from the whole blood. The polymorphism of TYMS-GSTP1 gene was detected by real-time pyrosequencing technique, and the patients were divided into two groups. To investigate the relationship between the polymorphism of TYMSN GSTP1 gene and the sensitivity of PP/PC regimen. Results 1. Genotypic analysis: there were three genotypes at the 105th amino acid locus of the GSTP1 gene. The frequency of genotype distribution was as follows: a / A / A / A = A / P / G ~ (36.3) and G / G / G ~ (3.3), respectively. According to the number of 28bp tandem repeats in the 5'#en0# region, the TYMS gene was divided into 3 types: 2R / 2R / 2R / 3.3R = 43.43.4R / 3R = 53.33.30.14 cases were immunohistochemically. There was a negative correlation between TYMS 2R / 3R genotype and TS protein expression (緯 -0.757P0.036N. 3). In univariate analysis, there was a negative correlation between TYMS 2R / 3R genotype and TS protein expression (緯 0.757P0.036N. 3). In univariate analysis, there was a negative correlation between TYMS 2R / 3R genotype and TS protein expression (緯 -0.757P0.036N. 3). The recent effective rate (58.3%) was significantly higher in patients with A / A genotype than in patients with A / A genotype. The median PFS of patients with G allele was longer than that of patients with A / A genotype (5.7-month vs.4.0 month, P0.047). In addition, the age of the patients was higher than that of the patients with G allele. Degree of differentiation, clinical stage, In univariate analysis, there was no significant difference between the genotype of TYMS and the short-term effective rate (P 0.05), but there was a significant difference between the genotype and PFS. The median PFS of the patients with 3R / 3R of TYMS genotype was less than 2R / 3R. Patients with genotype (4.3-month vs7.8 month P 0.036) 5. Cox proportional risk model multivariate analysis of gender, The relationship between genotype and PFS, sex and genotype were correlated with PFS. The risk of disease progression in women was 2.12 times higher than that in men. The risk of disease progression in patients with A / A genotype was 1.537 times as high as that in patients with G allele. The risk of disease progression was 1.763 times that of patients with 2R / 3R genotype. Conclusion the short term curative effect and PFS of patients with G allele carrying G allele in PP/PC regimen of late stage NSCLC patients were higher than those of patients with 2R / 3R genotype of TYMS gene 5'#en3# region, which were longer than those of 3R / 3R patients with TYMS gene 5'#en3# region genotype, conclusion\\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%\%. GSTP 1 + I105V) and TYMS 2R / 3R genotype polymorphism can be used as a reference index to predict the combination of pemetrexide and platinum regimen in patients with advanced non-small cell lung adenocarcinoma. The TYMS 2 R / 3 R genotype may reflect the content of TYMS enzyme in tumor cells.
【學(xué)位授予單位】：南華大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R734.2

【共引文獻(xiàn)】

相關(guān)期刊論文 前2條

1 Mariusz Panczyk;;Pharmacogenetics research on chemotherapy resistance in colorectal cancer over the last 20 years[J];World Journal of Gastroenterology;2014年29期

2 張鳳岐;沈燕;王珊珊;衛(wèi)肖;;外周血中TYMS和ERCC1基因多態(tài)性對胃腸道腫瘤患者化療療效的評估[J];腫瘤防治研究;2014年08期

，

本文編號：1615881