肝细胞癌ASC基因启动子区甲基化及其mRNA表达研究

目的:探讨肝细胞肝癌(HCC)ASC基因启动子区甲基化与mRNA表达及其临床病理特征的关系.方法:运用甲基化特异性聚合酶链反应(MSP)和实时荧光定量PCR技术,检测58例肝细胞癌及其相应癌旁组织、15例肝硬化肝组织、5例慢性病毒性肝炎肝组织和5例正常肝组织中ASC基因启动子区甲基化状态及其mRNA的表达水平.结果:58例肝细胞癌组织中有40例(69.0%)发生ASC基因启动子区甲基化,其相应癌旁组织中有27例(46.6%)发生该基因启动子区甲基化,而在肝硬化、肝炎和正常肝组织中均未检测到该基因启动子区甲基化.ASC基因在肝细胞癌组织中甲基化频率高于其相应癌旁组织(P=0.015).ASC基因启动子区甲基化与肿瘤直径(P=0.001)、生长方式(P=0.003)以及国际抗癌联盟第6版TNM(TNM6)分期(P=0.001)有关.以ASC基因在正常肝组织中的表达量为参照,58例肝细胞癌组织中有33例出现ASC基因mRNA低表达或表达缺失,其相应癌旁组织中有14例出现低表达或表达缺失,而在肝硬化及肝炎肝组织中ASC基因mRNA均呈正常表达.与癌旁组织相比,肝细胞癌组织中ASC基因mRNA表达明显下调(P<0.05).在发生ASC基因启动子区甲基化的40例肝细胞癌组织中有26例出现mRNA低表达.结论:ASC基因启动子区甲基化是肝细胞癌中的频发事件,可能在肝细胞癌的进展中起重要作用.     

RASSF1A和p16 转录本在非小细胞肺癌中的表达及启动子区甲基化

 目的 研究RASSF1A和p16基因在国人非小细胞肺癌（NSCLC）组织中的转录及启动子区甲基化情况，探讨其转录失活的机制，为NSCLC的诊断和治疗寻找新的途径。方法 应用半定量RTPCR和甲基化特异性PCR法分析96例NSCLC及远癌正常肺组织中RASSF1A和p16基因mRNA的表达和启动子区甲基化情况。结果 （1）53．12％（51／96）的NSCLC中RASSF1A表达明显下调或缺失；36．46％（35／96）的p16表达下调或缺失，而远癌正常肺组织均表达良好。（2）96例NSCLC中RASSF1A甲基化率48．96％（47／96），该基因表达明显下调或缺失的51例中39例（76．5％）出现甲基化，表达正常的45例中8例（17．8％）出现甲基化，两组对比差异有统计学意义（P〈0．05）；96例NSCLC中33例（34．38％）检测到p16启动予区甲基化，p16基因表达明显下调的35例中20例（57．1％）出现该基因CPG岛的甲基化，而表达正常的61例中13例（21．3％）出现甲基化，两组比较差异显著（P〈0．05）。96例远癌正常肺组织均未检测到此两基因启动子有甲基化。结论 RASSF1A和p16基因mRNA在国人NSCLC中较高比例的表达下调或缺失；甲基化可能是两基因表达失活的主要原因。     

非小细胞肺癌中FHIT基因异常甲基化对其蛋白、mRNA表达的影响

背景与目的 脆性组氨酸三联体(fragile histidine triad,FHIT)是一种新的抑癌基因,其启动子甲基化在肿瘤的发生和发展过程中发挥重要作用.本研究的目的 是通过检测非小细胞肺癌(non-small cell lung cancer,NSCLC)中抑癌基因FHIT启动子CpG岛异常甲基化和蛋白、转录表达情况及其相互关系,探讨FHIT基因在NSCLC发生发展中的作用.方法 应用甲基化特异性PCR(Methylation-specific PCR,MSP)、免疫印迹(Western Blot)及RT-PCR测定52例NSCLC组织及其癌旁正常组织(>5 cm)中FHIT的甲基化、蛋白表达和转录水平.结果 NSCLC癌组织中FHIT甲基化率为38.46%(20/52),在癌旁正常组织中FHIT甲基化率为7.6996(4/52),两者差异存在统计学意义(P<0.05);癌组织中FHIT蛋白表达率为28.8%(15/52),癌旁正常组织FHIT蛋白表达率为88.5%(46/52),两者差异存在统计学意义(P=0.000);FHIT mRNA在癌组织中表达率为51.9%(27/52),在癌旁正常组织中全部表达,且表达量明显高于癌组织(P=0.000).结论 在NSCLC中,FHIT基因启动子甲基化频率明显升高,其蛋白表达率明显下降,mRNA表达率下降,提示FHIT启动子甲基化在肺癌的发生和发展中起着一定作用,而且FHIT基因的甲基化与蛋白及mRNA的表达存在一定的关系.     

染色体3p区抑癌基因在非小细胞肺癌中的甲基化状况与临床意义

背景与目的 DNA甲基化是表观遗传学的一种调控机制,染色体3p区等位基因缺失是肺癌发生中较频繁和早期的事件之一。检测染色体3p区5个典型抑癌基因DLEC1、RASSF1A、hMLH1、RARβ和FHIT在非小细胞肺癌(non-small cell lung cancer,NSCLC)中的甲基化状况,分析其临床意义。方法取78例NSCLC患者术中癌组织及相应正常肺组织标本,采用甲基化特异性聚合酶链反应(methylation specific PCR,MSP)检测基因启动子区甲基化状况,RT-PCR和免疫组化检测DLEC1基因表达。结果 78例NSCLC组织中,DLEC1、RASSF1A、RARβ和hMLH1甲基化频率分别为41.03%、39.74%、30.77%和16.67%,与正常组织相比差异均具有统计学意义。FHIT基因在癌组织和正常组织均无甲基化。DLEC1甲基化与患者临床分期(P=0.011)和淋巴结转移相关(P=0.019),而RASSF1A、RARβ、hMLH1基因甲基化以及平均甲基化指数与临床病理特征无关联。56.41%(44/78)的NSCLC组织中发现DLEC1基因表达下调或缺失,且与启动子甲基化有关。结论 3p区抑癌基因甲基化是NSCLC发生中的重要分子事件,可能作为NSCLC早期诊断的潜在生物标记,新型抑癌基因DLEC1失活与启动子高甲基化有关。     

WWOX基因在贲门腺癌中的异常甲基化及其表达

目的:探讨贲门腺癌(gastric cardia adenocarcinoma,GCA)中WWOX( WW domain-containing oxidoreductase)基因启动子区及第1外显子区的甲基化状态及其对表达的影响,并分析贲门腺癌中WWOX与Smad4(mothers against decapentaplegic homolog 4)蛋白表达之间的关系.方法:分别应用甲基化特异性PCR和免疫组织化学法检测贲门腺癌组织及其相应癌旁组织中WWOX基因的甲基化和蛋白的表达情况:应用免疫组织化学法检测贲门腺癌组织及其相应癌旁组织中Smad4蛋白的表达.结果:贲门腺癌组织中WWOX基因启动子区(- 382～- 41 bp)及第1外显子区(- 27～+344 bp)的甲基化率[26.4％ (33/125)和23.2％ (29/125)]显著高于其相应的癌旁常组织(0％和0％)(P＜0.01),并与贲门腺癌TNM分期和上消化系统肿瘤家族史有关(P＜0.05).贲门腺癌组织中WWOX蛋白的表达阳性率显著低于相应癌旁组织(P＜0.01),WWOX蛋白的表达与WWOX启动子区和第1外显子区甲基化状态之间呈负相关(r=-0.216,r=-0.255,P＜0.05).贲门腺癌组织中Smad4蛋白表达的阳性率(47.2％)显著低于相应癌旁组织(94.4％)(P＜0.01),且与WWOX在贲门腺癌中的表达呈明显的正相关(r=0.622,P＜0.01).结论:WWOX基因启动子区及第1外显子区的高甲基化导致的基因表达下调可能在贲门腺癌中发挥重要作用.     

非小细胞肺癌EGFR启动子区甲基化和mRNA表达临床意义的探讨

目的:研究表皮生长因子受体(EGFR)的表达与非小细胞肺癌(NSCLC)组织学类型和淋巴结转移的关系,分析EGFR启动子区甲基化与其mRNA表达的关系.方法:应用免疫组织化学法检测60例非小细胞肺癌组织中EGFR的表达,统计EGFR与病理类型及淋巴结转移的关系.用实时定量PCR方法检测其中30例非小细胞肺癌组织和对应的癌旁组织中EGFR mRNA的表达,用甲基化特异性PCR(MSP)方法检测EGFR启动子区的甲基化状态.结果:鳞癌中EGFR阳性率为38.5％(10/26),明显低于腺癌中EGFR阳性率76.5％ (26/34),差异有统计学意义,x2=8.87,P=0.002 9;且有淋巴结转移的NSCLC中EGFR的阳性率为73.7％(28/38),而无淋巴结转移的NSCLC中EGFR的阳性率为45.5％(10/22),差异有统计学意义,x2=4.78,P=0.028.30例有癌旁组织的标本中,11例患者肿瘤组织EGFR的表达高于其癌旁组织;12例标本中存在肿瘤组织EGFR基因启动子区甲基化水平与EGFR mRNA表达呈负调节关系.结论:EGFR的表达与NSCLC的病理类型及淋巴结转移相关,部分NSCLC患者中存在EGFR基因启动子区甲基化水平与EGFR基因mRNA表达呈负调节关系.     

BRCA1基因甲基化及甲硫氨酸合成酶与乳腺癌发病的关系

背景与目的:启动子异常甲基化是肿瘤发生的早期事件,肿瘤组织中存在的DNA甲基化异常可以概括为广泛低甲基化伴局部高甲基化.甲硫氨酸合成酶(methionine synthase,MS)是参与甲基供体生成的关键酶,为DNA的甲基化提供甲基.本研究探讨抑癌基因BRCA1 mRNA在乳腺癌组织中的表达及启动子区甲基化状态,及MS基因mRNA表达与BRCA1基因甲基化的关系.方法:应用RT-PCR及甲基化特异性PCR(methylationspecific PCR,MSP)技术检测乳腺癌组织、相应癌旁组织(距癌>3 cm)和乳腺良性病变组织中BRCA1 mRNA的表达及其启动子甲基化状态,并检测MS mRNA的表达水平.结果:乳腺癌组织、癌旁组织及良性病变组织BRCA1mRNA表达差异有统计学意义(P<0.05);乳腺癌组织中BRCA1基因启动子区甲基化检出率明显高于癌旁组织和良性病变组织(χ2=7.631,P<0.05),BRCA1基因启动子区甲基化与散发性乳腺癌组织学分级、雌激素受体(estrogen receptor,ER)相关(P<0.05).乳腺癌组织MS基因表达量明显低于乳腺良性病变及乳腺癌旁组织(P<0.05).MS mRNA的表达与BRCA1基因甲基化的发生有相关性(r=0.419,P<0.05).结论:BRCA1甲基化能够增加乳腺癌的患病风险,MS基因可能通过影响部分肿瘤相关基因发生甲基化而调控其表达.     

胃癌组织中mRNA-375基因高甲基化及其表达的研究

目的:探讨胃癌组织中miRNA-375基因表达与基因甲基化调控的相关性.方法:2011年3月至8月在天津医科大学总医院通过胃镜检查收集90例新鲜组织活检标本,分为2组,胃癌组54例,非癌对照组36例.应用实时荧光定量反转录PCR检测miRNA-375基因表达,甲基化特异性PCR检测miRNA-375基因启动子区CpG岛甲基化.结果:胃癌组miRNA-375基因表达下调,与非癌对照组相比差异有统计学意义(P<0.05);胃癌组和非癌对照组 miRNA-375基因启动子区高甲基化阳性率分别为62.96%(34/54)和22.22%(8/36),差异有统计学意义(χ2=14.405, P<0.05).中高分化胃癌组织中miRNA-375基因表达高于低分化组,差异有统计学意义(t=2.634,P=0.011);miRNA-375基因启动子区甲基化阳性率中高分化组与低分化组分别为44.44%(8/18)和72.22%(26/36),差异有统计学意义(χ2=3.971,P=0.046).结论:癌组织中存在miRNA-375基因异常低表达及启动子区的高甲基化,miRNA-375基因高甲基化可能抑制miRNA-375基因表达,在胃癌发生发展中发挥重要作用.     

PTEN基因甲基化及其表达异常与胃癌的关系

目的：探讨PTEN基因表达、启动子区甲基化与胃癌及其临床病理特征的关系。方法：采用甲基化特异性PCR法（MSP）和逆转录聚合酶链反应（RT—PCR）法，分析胃癌组织及相应癌旁正常组织中PTEN基因启动子区甲基化及其mRNA表达情况。结果：48．2％（27／56）的胃癌组织和3．6％（2／56）的癌旁胃组织PTEN基因启动子区发生甲基化．癌组织PTEN基因启动子区甲基化率显著增高（P〈0．05）：其中，2例甲基化癌旁胃组织均为胃癌组织中有甲基化的病例．发生淋巴结转移的29例胃癌组织中．19例PTEN基因启动子甲基化；发生淋巴结转移的PTEN基因启动子甲基化显著高于无淋巴结转移组（P〈0．05）。RT—PCR结果显示，所有甲基化的胃癌组织中PTEN mRNA均无表达，结论：胃癌中PTEN基因mRNA失表达与其启动子区甲基化有关，这可能是胃癌发生、发展以及转移的原因之一。     

乳腺癌Runx3基因启动子甲基化状态及其与病理特征的关系

目的探讨乳腺癌组织中Runx3基因启动子甲基化状态及其与乳腺癌临床病理特征之间的关系。方法 2007年2月至2009年4月收集经病理确诊的56例乳腺癌患者癌组织及相应的癌旁组织。采用甲基化特异聚合酶链反应检测Runx3基因启动子区CpG岛的甲基化状态,并检测其对Runx3基因表达的影响和分析其与乳腺癌临床病理特征之间的关系。统计学分析采用χ2检验和Pearson相关分析法。结果乳腺癌组织中Runx3基因启动子区CpG岛甲基化率(55.4%)显著高于癌旁组织中的甲基化率(10.7%),二者之间差异有统计学意义(χ2=25.225,P=0.000)。Runx3基因的异常甲基化和乳腺癌患者的临床分期及淋巴结转移有关(P=0.018,P=0.010),但与患者的年龄、肿瘤直径大小及组织学类型无关(P0.050)。Runx3mRNA表达与Runx3启动子甲基化呈弱相关(r=0.343,P=0.010)。结论 Runx3基因启动子甲基化状态导致Runx3基因mRNA表达降低或缺失。Runx3基因启动子区甲基化可能是导致Runx3基因在乳腺癌中失活的分子机制之一。     

Epigenetic inactivation of the RAS-effector gene RASSF2 in lung cancers

RASSF2, a member of the RAS association domain family 1 (RASSF1), is a candidate tumor suppressor gene (TSG) that is silenced by promoter hypermethylation in several human cancers. In this study, we examined the expression of RASSF2 mRNA and the promoter methylation status in lung cancer cell lines and in tumor samples of 106 primary non-small cell lung cancers (NSCLCs) by methylation-specific PCR. RASSF2 expression was absent in 26% of small cell lung cancers (SCLCs; n=27 lines) and 50% of NSCLCs (n=42 lines). Promoter methylation of RASSF2 was found in 18% of the SCLC cell lines (n=22) and 62% of the NSCLC cell lines (n=26), and the methylation status was tightly associated with the loss of RASSF2 expression. RASSF2 expression was restored by treatment with 5-aza-2-deoxycytidine and/or trichostatin-A in the NSCLC cell lines which were absent of the expression. RASSF2 methylation was found in 31% of primary NSCLC tumors, and methylation was more frequent in the specimens from non-smokers (18 of 40, 45%) than in the specimens from smokers (15 of 66, 23%, P=0.014). We also examined the association of RASSF2 methylation with mutations of KRAS and EGFR and with promoter hypermethylation of RASSF1A; however, we could not find a significant association between RASSF2 methylation and these genetic and epigenetic changes. Our results indicate that aberrant methylation of the RASSF2 gene with the subsequent loss of RASSF2 expression plays an important role in the pathogenesis of lung cancers.     

Clinical outcomes of downregulation of E-cadherin gene expression in non-small cell lung cancer

Objective: To investigate the promoter methylation status of the E-cadherin gene in non-small cell lung cancer(NSCLC) and its association with clinical pathological parameters, and to explore the relationship betweendownregulation of E-cadherin gene expression and the methylation status of its promoter region. Methods:Nested methylation-specific PCR was performed to examine CpG methylation within the 5’ CpG island of theE-cadherin gene in lung cancer and para-cancerous tissue from 37 patients with primary non-small cell lungcancer. Quantitative real-time PCR was performed to measure the level of E-cadherin mRNA. Results: Ofthirty-seven cases, 12 (32.4%) samples showed aberrant CpG methylation in tumor tissues compared with thecorresponding normal tissues. In addition, a reduction in E-cadherin mRNA levels was observed in 11 of the12 (91.7%) tumor tissues carrying a methylated E-cadherin gene. However, only 10 (43.5%) cases displayedreduced mRNA levels in tumor tissues from the remaining 23 cases (excluding 2 samples from which mRNA wasunavailable) without methylation events. Downregulation of E-cadherin gene expression significantly correlatedwith the promoter methylation status of this gene. Conclusion: These results provide strong evidence that themethylation status of E-cadherin gene contributes to a reduction in the expression of E-cadherin mRNA, andmay play a role in the development and progression of NSCLC.     

凋亡蛋白酶活化因子-1基因在贲门腺癌中的甲基化状态及其临床意义

目的:探讨贲门腺癌(gastric cardiac adenocarcinoma,GCA)中凋亡蛋白酶活化因子-1(apoptosis protease activating factor-1,Apaf-1)基因启动子区甲基化状态及其与果蝇zeste基因增强子人类同源物2(enhancer of zeste homolog 2,EZH2)蛋白表达之间的相关性.方法:应用甲基化特异性PCR(methylation specific polymerase chain reaction,MSP)检测GCA组织及癌旁组织中Apaf-1基因甲基化状态,应用免疫组织化学法检测GCA组织及癌旁组织中Apaf-1和EZH2蛋白的表达情况.结果:GCA组织中Apaf-1基因甲基化率显著高于癌旁组织[49.6％ (62/125)vs4.0％(5/125),P＜0.01],Ⅲ期和Ⅳ期GCA组织中Apaf-1基因甲基化率显著高于Ⅰ期和Ⅱ期(58.8％vs 38.6％,P＜0.05),但GCA组织中Apaf-1基因甲基化率与GCA的组织学分化程度无关(P＞0.05).GCA组织中Apaf-1蛋白表达阳性率显著低于相应癌旁组织(39.2％ vs 96.0％,P＜0.O1),且与Apaf-1基因甲基化状态相关.GCA组织中EZH2蛋白表达阳性率显著高于相应癌旁组织(74.4％vs 11.2％,P＜0.01),且与Apaf-1蛋白的表达呈负相关.结论:GCA组织中Apaf-1基因启动子区呈高甲基化,Apaf-1和EZH2蛋白可能共同参与了GCA的发展.     

Promoter hypermethylation is the predominant mechanism in hMLH1 and hMSH2 deregulation and is a poor prognostic factor in nonsmoking lung cancer.

PURPOSE AND EXPERIMENTAL DESIGN: The etiologic association and prognostic significance of mismatch repair gene/protein alterations have never been examined in nonsmoking lung cancer. Therefore, we investigated protein expression and promoter hypermethylation of hMLH1 and hMSH2 genes in the tumor specimens from 105 nonsmoking female non-small cell lung cancer (NSCLC) patients. Immunohistochemistry and restriction enzyme-based multiplex PCR were used to examine the protein expression and promoter hypermethylation, respectively. The occurrence of gene/protein alteration for each gene was compared with the patients' clinicopathologic variables as well as the overall survival and cancer-specific survival rates. RESULTS: Protein expression alteration and promoter hypermethylation were observed in 66% to 67% and 30% to 34% of tumor specimens for hMLH1 and hMSH2 genes, respectively. Loss of hMLH1 and hMSH2 protein expression was significantly associated with their promoter hypermethylation (P < 0.0001 and P = 0.049). The overall survival and cancer-specific survival rates were significantly lower in patients with promoter hypermethylation of hMSH2 gene than in those without hypermethylation (P = 0.038 and P = 0.004). The poor prognosis was still especially significant in adenocarcinoma (P = 0.035 and P = 0.061) and early-stage NSCLC patients (P = 0.067 and P = 0.041). CONCLUSION: Our data suggest that hMLH1 is the major altered mismatch repair gene involved in nonsmoking NSCLC tumorigenesis and that promoter methylation is the predominant mechanism in hMLH1 and hMSH2 deregulation. In addition, promoter methylation of the hMSH2 gene may be a potential prognostic factor in nonsmoking female lung cancer.     

肺癌组织细胞FHIT 基因启动子甲基化和转录表达

 目的 探讨FHIT（fragile histidine triad，脆性组氨酸三联体）基因表达水平及其启动子CpG岛甲基化状态与肺癌发生发展的关系。方法 用实时定量PCR检测FHIT mRNA在肺癌组织、肺癌旁组织与去甲基化剂5-氮杂-2’-脱氧胞苷（5-Aza-2’-deoxycytidine、5-Aza—CdR）处理前后A549细胞株中的表达，用甲基化特异性PCR（MS-PCR）检测FHIT启动子CpG岛甲基化状态。结果 FHIT mRNA在肺癌旁组织中全部表达，在肺癌组织中表达缺失率为48．89％（22／45），且表达量低于正常肺组织（t=-15．851，P〈0．001），但在不同年龄和性别、肿瘤大小、恶性程度、肿瘤分类的差异无显著性；FHIT基因启动子在肺癌组织中发生甲基化的频率为40％（18／45）、在癌旁组织中频率8．7％（2／23）（X^2=7．184，P〈0．01），18份启动子区甲基化的肺癌标本中，10份同时伴有mRNA表达缺失。结论 在肺癌组织中，FHIT基因启动子甲基化频率明显升高，其表达缺失或下调，提示FHIT启动子甲基化可在肺癌发生和发展中起一定作用。     

卵巢上皮性癌TGFBI基因启动子甲基化与CyclinD1蛋白表达的关系

研究TGFBI基因启动子甲基化与CyclinD1蛋白表达在卵巢上皮性癌组织中关系,探讨TGFBI基因启动子甲基化在卵巢上皮性癌形成过程中的影响及意义。方法:用甲基化PCR的方法对20例正常卵巢上皮性组织（A组）,20例良性卵巢上皮性肿瘤组织（B组）,30例卵巢上皮性癌组织（C组）中TGFBI基因启动子甲基化进行检测,用免疫组化SP方法检测上述标本中CyclinD1蛋白的表达的情况。结果:1）C组TGFBI基因启动子甲基化频率高于B组及A组（P<0.05）;2）CyclinD1蛋白在卵巢上皮组织中的表达为:C组>B组>A组,各组之间差异均有统计学意义（P<0.016 7）;3）卵巢上皮性癌组织中CyclinD1蛋白表达增高与TGFBI基因启动子发生甲基化有关（r=0.505,P<0.05）。结论:TGFBI基因DNA启动子发生甲基化可能上调CyclinD1蛋白的表达,刺激细胞异常增殖。该机制可能参与卵巢上皮性癌的发生发展。      

Clinical significance of aberrant methylation of prostaglandin E receptor 2 (PTGER2) in nonsmall cell lung cancer: association with prognosis, PTGER2 expression, and epidermal growth factor receptor mutation

BACKGROUND.: The expression of prostaglandin E receptor 2 (PTGER2) affects the biologic behavior of various types of malignant tumors. Recently, transactivation of both PTGER2 and epidermal growth factor receptor (EGFR) has been reported in some tumors. METHODS.: PTGER2 gene expression and possible aberrant methylation of the PTGER2 gene were investigated in 10 nonsmall cell lung cancer (NSCLC) cell lines, 233 primary tumors, and 168 adjacent nonmalignant lung tissues. They were analyzed with reference to an association with EGFR mutation in 133 clinical lung adenocarcinomas and were correlated with patient survival. RESULTS.: Down-regulation of PTGER2 expression was observed in 8 of 10 NSCLC cell lines. Demethylation of 5 expression-negative cell lines restored the expression of PTGER2. Aberrant methylation of the PTGER2 gene was reversely concordant with its messenger RNA expression. PTGER2 methylation was detected in 137 of 233 NSCLC specimens (58%) but was detected in only 2 of 168 nonmalignant lung tissues (1%). Both NSCLCs and adenocarcinomas that had PTGER2 methylation predicted a significantly better prognosis than those without PTGER2 methylation (P = .0051 and P = .0171, respectively). PTGER2 methylation was present with greater frequency in tumors with EGFR mutation than in non-EGFR mutated tumors (P = .0095), and the significance of the correlation was independent after adjusting for sex and smoking status (P = .0144). CONCLUSIONS.: Aberrant methylation of the PTGER2 gene was observed frequently in NSCLC tissues and was associated with the presence of EGFR mutation and a better prognosis. Cancer 2008. (c) 2008 American Cancer Society.