O^6-甲基鸟嘌呤-DNA甲基转移酶基因多态性与新疆哈萨克族食管癌易感性关系的研究

目的 为探讨O6-甲基鸟嘌呤-DNA甲基转移酶(MGMT)基因多态性与新疆哈萨克族食管癌易感性的关系. 方法 运用病例-对照研究的方法,PCR-RFLP技术检测新疆哈萨克族食管癌51例及非癌对照109例的MGMT 84C>T和MGMT 135G>T单核苷酸多态(SNPs)的基因型. 结果 MGMT 84C>T位点的三种基因型CC,CT,TT,在哈萨克族食管癌中所占比例分别为76.5%(39/51) 、17.6%(9/51) 、5.9%(3/51),对照组分别为77.0%(84/109)、18.3%(20/109)、4.6%(5/109),两组间分布差异不显著(P=0.938,P>0.05);MGMT 135G>T位点的三种基因型GG,GT,TT,在哈萨克族食管癌中所占比例分别为90.2%(46/51)、7.8%(4/51)、2.0%(1/51),对照组分别为82.6%(90/109)、16.5%(18/109)、0.9%(1/109),两组间分布差异不显著(P=0.295,P>0.05);MGMT 84C>T位点和MGMT 135G>T位点联合分析,在食管癌组0突变等位基因与1-4突变等位基因所占比例分别为68.6%(35/51)、31.4%(16/51);对照组分别为:63.3%(69/109)、36.7%(40/109),两组间分布差异也不显著(P=0.511,P>0.05). 结论 MGMT 84C>T和MGMT 135G>T SNPs与哈萨克族食管癌易感性可能无关联.     

非小细胞肺癌患者血清O6-甲基鸟嘌呤-DNA-甲基转移酶基因异常甲基化检测及其临床意义

目的 探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)患者血清中O6-甲基鸟嘌呤-DNA-甲基转移酶(O6-methylguanine-DNA-methyhransferase,MGMT)基因启动子区域甲基化的改变状况及其临床意义.方法 基因测序法检测62例NSCLC患者、30例肺部良性疾病患者和16例健康体检者血清中MGMT基因启动子区域甲基化状况,并分析其与临床特征的关系.结果 NSCLC患者血清MGMT基因甲基化检出率为27.42%(17/62),而肺部良性疾病患者和健康体检者血清未检出MGMT基因甲基化(Fisher精确概率法,P＜0.01).MGMT基因甲基化检出率与NSCLC患者年龄、性别、病理类型、分化程度无明显相关,但在晚期患者中检出率较高(P＜0.05).MGMT基因甲基化患者吸烟指数(年·支)明显高于非甲基化患者(P＜0.01).结论 MGMT基因异常甲基化可能在NSCLC发生、发展中起重要作用,有望成为NSCLC辅助诊断的分子标记.     

老年性大肠癌中MGMT的表达及临床意义

目的探讨MGMT在老年性大肠癌中的表达及其临床意义。方法采用免疫组化方法（SABC法）检测13例正常大肠黏膜、28例大肠腺瘤和86例大肠癌标本中MGMT的表达情况。结果在正常黏膜组、腺瘤组和肠癌组中MGMT阳性率分别为7．69％、21．43％和54．65％，其中肠癌组和正常黏膜组、腺瘤组比较均有显著性差异（P〈0．05）；MGMT在有淋巴结转移组与无淋巴结转移组中阳性率比较差异显著（P〈0．05），在癌组织浸润深度达浆膜组和深肌层组比较也有显著性差异（P〈0．05），但MGMT在大肠癌中的表达与性别、部位和病理类型相关性不明显。结论MGMT在老年性大肠癌的发生中可能起重要作用，检测大肠癌组织中MGMT蛋白对指导治疗及评价预后有重要的临床意义。     

MGMT和ERCC1在胃癌及癌前病变中的表达及意义

目的探讨DNA损伤修复基因产物O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）与切除修复交叉互补基因1（ERCC1）的表达,及其与胃癌发生及生物学行为的关系。方法采用免疫组化SP法检测MGMT和ER-CC1的表达情况,并与临床病理特征相比较。结果 MGMT蛋白在轻度异型增生胃黏膜的表达率高于早期胃癌及进展期胃癌,ERCC1在正常胃黏膜的表达率高于早期胃癌及进展期胃癌。MGMT表达与胃癌分化程度、淋巴结转移有关,ERCC1与分化程度、浸润深度、淋巴结转移有关。胃癌中MGMT表达与ERCC1表达呈正相关。结论 MGMT、ERCC1可能在胃癌发生中起重要作用,有可能成为判断胃癌生物学行为的有用指标。     

非小细胞肺癌DNA甲基转移酶及基因p53表达与预后的关系

目的 探讨DNA修复酶O6-甲基鸟嘌呤DNA甲基转移酶(MGMT)及抑癌基因p53在非小细胞肺癌(NSCLC)中的表达及其与预后的关系. 方法 采用免疫组织化学SP法检测110例NSCLC患者及20例肺部良性病变患者术后肺组织中MGMT及p53的表达,并观察110例NSCLC根治术后患者的生存期. 结果 110例NSCLC患者及20例肺良性病变患者组织中MGMT蛋白阳性表达率分别为41.8%(46/110)和80%(16/20),p.53蛋白的阳性表达率分别为56.4%(62/110)和0%(0/20)例,MGMT蛋白表达与淋巴结转移及吸烟史相关(x2值为12.107和6.512,均P<0.05),p53蛋白表达亦与淋巴结转移及吸烟史相关(X2值为6.330和7.909,均P<0.05),MGMT和p53蛋白表达呈负相关(Rs=-0.592,P<0.05).110例患者的5年生存率为10.9%(12/110),中位生存期为(30.4±0.6)个月;46例MGMT表达阳性的患者5年生存率为0%(0/110),中位生存期为(25.9±0.4)个月,均低于64例MGMT表达阴性患者的5年生存率(18.8%,12/64)和中位生存期[(32.4±0.7)个月],差异有统计学意义(x2=23.569,P<0.05).62例053表达阳性患者的5年生存率为4.8%(3/62),中位生存期为(30.4±1.2)个月,均低于48例p53表达阴性患者的5年生存率(18.8%,9/48)和中位生存期[(30.5±1.1)个月],差异有统计学意义(x2=5.521,P<0.05). 结论 NSCLC患者体内MGMT表达缺失可能与突变型p53的表达水平有关,且与肺癌的发生、发展及预后相关.     

非小细胞肺癌DNA甲基转移酶及基因p53表达与预后的关系

Objective To investigate the expression and role of O~6-methylguanine DNA methyltransferas(MGMT) and p53 in non-small cell lung cancer(NSCLc)and the association with prognosis. Methods Immunohistochemical method was used to investigate the expression of MGMT and p53 in NSCLC specimens from 110 cases and in 20 cages of benign lung diseases as the control.The association of their expression with the prognosis of the 110 patients was evaluated. Results The positive expression of MGMT in NSCLC and benign lung diseases was 41.8%(46/110)and 80%(16/20)(x2=9.89,P<0.05),respectively.The positive expression of p53 in NSCLC and benign lung diseases were 56.4%(62/110)and 0%(0/20)(x2=21.551,P<0.05),respectively.There was a significant association between expression of MGMT with smoking,and lymph node metastasis (x2=12.107,P<0.05;x2=6.512P<0.05).There was also a significant association between expression of p53 with smoking and lymph node metastasis(x2=6.330,P<0.05;x2=7.909,P<0.05).A negative correlation was observed between the expression of MGMT and that of p53 protein in NSCLC(R_S=-0.592,P<0.05).The 5-year survival rate and median survival time of 110 cages was 10.9%(12/110),and(30.4±0.6)months.In 46 cases with positive expression of MGMT the 5-year survival rate was 0%(0/110)and median survival was(25.9±0.4)months,which were lower than those in the 64 patients with negative expression of MGMT [18.8%(12/64),(32.4 ±0.7)months],Log rank test x2=23.569,P<0.05.in the 62 patients with positive expression of p53.the 5-year survival rate and modian survival were 4.8%(3/62)and(30.4±1.2)months,which were lower than those in the 48 cases with negative expression of p53[18.8%(9/48),(30. 5± 1.1 ) months], Log rank test X2 =5. 521, P <0. 05. Conclusion The loss of expression of MGMT may lead to activation of the wild-type p53. They may participate in lung carcinomatosis, and may predict prognosis in patients with NSCLC.     

非小细胞肺癌DNA甲基转移酶及基因p53表达与预后的关系

Objective To investigate the expression and role of O~6-methylguanine DNA methyltransferas(MGMT) and p53 in non-small cell lung cancer(NSCLc)and the association with prognosis. Methods Immunohistochemical method was used to investigate the expression of MGMT and p53 in NSCLC specimens from 110 cases and in 20 cages of benign lung diseases as the control.The association of their expression with the prognosis of the 110 patients was evaluated. Results The positive expression of MGMT in NSCLC and benign lung diseases was 41.8%(46/110)and 80%(16/20)(x2=9.89,P<0.05),respectively.The positive expression of p53 in NSCLC and benign lung diseases were 56.4%(62/110)and 0%(0/20)(x2=21.551,P<0.05),respectively.There was a significant association between expression of MGMT with smoking,and lymph node metastasis (x2=12.107,P<0.05;x2=6.512P<0.05).There was also a significant association between expression of p53 with smoking and lymph node metastasis(x2=6.330,P<0.05;x2=7.909,P<0.05).A negative correlation was observed between the expression of MGMT and that of p53 protein in NSCLC(R_S=-0.592,P<0.05).The 5-year survival rate and median survival time of 110 cages was 10.9%(12/110),and(30.4±0.6)months.In 46 cases with positive expression of MGMT the 5-year survival rate was 0%(0/110)and median survival was(25.9±0.4)months,which were lower than those in the 64 patients with negative expression of MGMT [18.8%(12/64),(32.4 ±0.7)months],Log rank test x2=23.569,P<0.05.in the 62 patients with positive expression of p53.the 5-year survival rate and modian survival were 4.8%(3/62)and(30.4±1.2)months,which were lower than those in the 48 cases with negative expression of p53[18.8%(9/48),(30. 5± 1.1 ) months], Log rank test X2 =5. 521, P <0. 05. Conclusion The loss of expression of MGMT may lead to activation of the wild-type p53. They may participate in lung carcinomatosis, and may predict prognosis in patients with NSCLC.     

食管癌患者O6-烷基鸟嘌呤-DNA烷基转移酶基因多态性研究

目的　检测中国食管癌高发区居民和高加索居民AGT     

食管癌患者谷胱甘肽—S转移酶的表达及临床意义

用人体胎盘型ＧＳＴ－π抗体，按ＡＢＣ免疫组织化学技术，检测了５０例食管癌、６８例癌旁组织和５１例正常对照组。并对其中３０例食管癌和２０例正常组进行了组织和血清ＧＳＴ活性检测。结果表明：正常食管组织ＧＳＴ－π阳性率为３．９２％，不典型增生组为７７．９４％，食管癌组为８６％。３０例食管癌组织和血清ＧＳＴ活性均值分别为：２．３９３±１．２１８和１６．６２０±４．４５０，而２０例正常组织和血清ＧＳＴ均值分别为：１．０６４±０．４９４和１３．４４０±４．００４，两组间差异显著（Ｐ＜０．０１）。ＧＳＴ－π在食管癌患者的表达为研究其发病机理和早期诊断提供了新的酶学指标。     

脑胶质瘤MGMT基因表达及启动子甲基化与患者临床预后关系的观察．

目的 探讨O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT）基因表达及启动子甲基化与脑胶质瘤患者临床预后的关系。方法 选取郑州大学人民医院神经外科2007年4月至2009年4月收治的同意接受脑胶质瘤个体化综合治疗且有完整病历资料的患者78例,根据脑胶质瘤MGMT基因表达及启动子甲基化情况分组,术后均采用同步放化疗,观察患者近期疗效、无进展生存时间及安全性,比较各组间疗效。两组间均数比较采用独立样本t检验,计数资料采用R×C表χ2检验,采用Kaplan-Meier方法绘制生存曲线,并采用Log-rank检验对其生存曲线进行分析。结果 MGMT基因启动子甲基化状态与MGMT蛋白表达呈负相关（r=-0.514,P〈0.05）。MGMT基因启动子甲基化组近期客观疗效明显优于MGMT基因启动子非甲基化组（χ2=47.890,P=0.000）;MGMT蛋白低表达组近期客观疗效明显优于MGMT蛋白高表达组（χ2=30.032,P=0.000）。MGMT基因启动子甲基化患者生存期明显长于非甲基化组（χ2=21.405,P〈0.05）,MGMT蛋白低表达患者生存期明显长于MGMT蛋白高表达组（χ2=18.643,P〈0.05）;MGMT基因启动子甲基化组客观有效率81.0%（34/42）优于MGMT蛋白低表达组74.4%（29/39）。患者均未出现明显不良反应。结论 脑胶质瘤MGMT基因表达及启动子甲基化与患者应用尼莫司汀＋替莫唑胺会师化疗同步适行放疗治疗预后密切相关,且MGMT甲基化对判断恶性胶质瘤患者预后吻合性更高,为临床制订有效的个体化疗方案提供参考。     

抑癌基因PTEN在食管癌中的表达及其临床意义

目的　研究食管癌中第 10号染色体丢失的张力蛋白同源的磷酸脂酶基因 (PTEN基因 )的表达及其临床意义。方法　用免疫组化方法检测 68例食管癌和癌旁正常组织中PTEN蛋白的表达水平。结果　食管癌中PTEN蛋白表达率为 70 .6% ,而癌旁正常组织为 10 0 % ,PTEN蛋白表达与肿瘤分化程度、浸润深度、淋巴结转移及TNM分期相关 (P <0 .0 5 )。PTEN蛋白在高中低分化组的阳性表达率分别为 90 .17%、66.67%和 5 0 %。单变量分析PTEN蛋白阳性表达组 3、5年生存率分别为 70 .3 %和 5 4.6% ,高于阴性表达组的 40 .2 5 %和 16.1%。经long rank时序检验差异有显著性(P =0 .0 2 5 8) ,Cox回归模型多变量分析显示 ,PTEN是一个独立预后指标 (P =0 .0 12 )。结论　从蛋白水平证明PTEN基因表达缺失或降低与食管癌的发生发展有关 ,PTEN蛋白表达的检测可能成为判断食管癌细胞生物学行为及部分患者预后的参考指标之一     

食管鳞癌组织中Smac、survivin的表达及其临床意义

目的 探讨Smac及survivin在食管鳞癌中的表达变化及其对食管癌预后的判断价值.方法 采用免疫组化方法 测定食管鳞癌组织及癌周正常食管组织中的Smac、survivin.结果 Smac在癌周正常食管组织中阳性表达高于在癌组织中的表达,survivin在癌周正常食管组织中阳性表达低于在癌组织中的表达;Smae在长期生存的食管癌患者中多呈高表达,survivin多呈低表达.Smac与survivin在食管鳞癌中的表达呈负相关(r=-0.288,P=0.013).结论 Smae及survivin可能是食管鳞癌细胞凋亡信号传导网络中的重要因子,是判断食管鳞癌预后的重要指标.     

Expression of midkine and its clinical significance in esophageal squamous cell carcinoma

AIM: TO investigate the expression of midkine in esophageal squamous cell carcinoma (ESCC) and analyze its relationship with clinicopathological features. METHODS: RT-PCR and immunocytochemical staining were used to detect the expression of midkine mRNA and protein in EC109 cells, respectively. Then the expression of midkine in 66 cases of ESCC samples were detected by immunohistochemistry using monoclonal antibodies against human midkine. RESULTS: Midkine was expressed in EC109 cell by RT-PCR and immunocytochemistry. The immunoreactivity was detected in 56.1% (37/66) of the ESCC samples. The expression of midkine was found in cytoplasm of tumor cells. Notably, the intensity of midkine was stronger at the area abundant in vessels and the invading border of the tumors. Midkine was more intensely expressed in well differentiated tumors (76.9%) than in moderately and poorly differentiated tumors (43.1% and 41.2%, respectively) (P<0.05). There was no statistically significant correlation between midkine expression and gender, age, clinical stage, lymph node metastasis or survival in ESCC. CONCLUSION: Midkine is overexpressed in ESCC. It may play a role in tumor angiogenesis and invasion. The expression of midkine is correlated with tumor cell differentiation in ESCC. The more poorly tumor cells differentiate, the weaker midkine expresses.     

Expression level and clinical significance of LncRNA HOXA11-AS in esophageal squamous cell carcinoma patients

正Objective To explore the expression of long noncoding RNA(lncRNA)HOXA11-AS in esophageal squamous cell carcinoma tissues and the relationship of HOXA11-AS level with clinical outcomes.Methods Quantitative real-time polymerase chain reaction(qRTPCR)was applied to detect the expression level of HOXA11-AS in cell lines HET-1A,EC9706,EC109,and in tumor tissue and paired adjacent tissue samples     

Expression and clinical significance of CtBP2 in human esophageal squamous cell carcinoma

<正>Objective To explore the expression of C-terminal binding protein 2(Ct BP2)in human esophageal carcinoma and its relationship with clinicopathological parameters and survival.Methods The expression levels of CtBP2 in eight cases of fresh frozen specimens of esophageal squamous cell carcinoma(ESCC)and the adjacent e-     

食管鳞癌组织中Survivin、Bcl-2蛋白的表达及意义

目的 探讨食管鳞癌中Survivin、Bcl-2蛋白的表达及其临床意义.方法 应用免疫组织化学SP法检测39例食管鳞癌组织、23例不典型增生组织及39例正常食管黏膜组织中Survivin、Bcl-2蛋白表达情况.结果 Survivin蛋白在癌组织中表达率为59.0%(23/39),Survivin蛋白的表达与肿瘤的临床分期、淋巴转移关系密切(P均＜0.05).Bcl-2蛋白在癌组织、癌旁不典型增生组织中的表达率为69.2%(27/39)、21.7%(5/23),Bel-2蛋白的表达与肿瘤组织的分化程度、临床分期、淋巴结转移有关(P均＜0.05);Survivin蛋白与Bcl-2蛋白表达呈正相关(r=0.46,P＜0.01).结论 Survivin蛋白和Bel-2蛋白的表达在食管癌的发生、发展中起重要作用.     

声门上型喉癌中乙酰肝素酶的表达及意义

目的探讨乙酰肝素酶(HPA)在声门上型喉癌组织中的表达及其临床意义。方法应用免疫组化技术检测HPA蛋白在60例声门上型喉癌组织和癌旁组织、10例正常喉组织中的表达情况。结果60例癌组织中,27例(45.0%)HPA蛋白阳性表达,癌旁组织中仅3例(5.0%)阳性表达,10例正常喉组织均为阴性表达。HPA蛋白的表达与TNM分期、颈淋巴结转移率、复发率及5a生存率有关(P<0.05)。结论声门上型喉癌组织中HPA蛋白高表达,并与肿瘤的侵袭转移、复发、预后有关。     

食管鳞癌组织VCAM-1和Survivin的表达及意义

目的探讨血管细胞黏附分子1（VCAM-1）和Survivin与食管鳞癌细胞发生、发展与转移的关系。方法采用免疫组化法检测24例正常食管黏膜、94例食管鳞癌组织中Survivin和VCAM-1的表达情况。结果VCAM-1和Survivin在癌组织中的表达率明显高于正常食管黏膜,其中VCAM-1表达与淋巴结转移、浸润深度和临床分期等因素有关（P均〈0．05）;Survivin表达与浸润深度有关（P〈0．01）;VCAM-1和Survivin在癌组织中的表达无相关性。结论VCAM-1和Survivin在食管鳞癌中高表达,二者在食管鳞癌的发生、发展过程中具有重要作用,可作为评价食管鳞癌生物学行为的指标。     

Expression of ANCR in nasopharyngeal carcinoma patients and its clinical significance

Anti-differentiation non-coding RNA (ANCR), a long non-coding RNA, is involved in the development, progression and metastasis of various human cancers. However, its clinical significance in nasopharyngeal carcinoma (NPC) still remains unknown. This study aimed to investigate ANCR expression and its clinical significance in NPC.Totally, 96 NPC tissues and 24 non-cancerous nasopharyngeal mucosa tissues were used. The levels of ANCR were determined by qRT-PCR. Relationship of ANCR with patient clinical characteristics, disease-free survival and overall survival (OS) was evaluated.ANCR expression was increased in NPC tissues compared to non-cancerous nasopharyngeal mucosae. ANCR expression was significantly related to lymph node metastasis, clinical stage, and tumor differentiation (P < .05). Kaplan-Meier survival analysis revealed that high level of ANCR expression was significantly associated with poor disease-free survival but not with OS in NPC patients. Univariate analysis showed a significant association between increased ANCR expression and adverse OS (P < .05), but multivariate analysis suggested that ANCR could not be used as an independent prognostic factor for NPC patients.ANCR is involved in the development and progression of NPC, but whether it can be used as an effective therapeutic target for NPC needs further study.     

MMP-2、TIMP-4在食管鳞状细胞癌中的表达及意义

目的 探讨食管鳞状细胞癌(ESCC)组织中基质金属蛋白酶2(MMP-2)及其特异性抑制剂基质金属蛋白酶抑制剂4(TIMP-4)的表达及其与临床病理参数的相关性.方法 选取经病理证实的ESCC组织68例及正常食管组织12例,免疫组化方法检测MMP-2与TIMP-4的表达.结果 MMP-2及TIMP-4在ESCC中阳性表达率明显高于正常食管组织(P<0.05);MMP-2表达与ESCC的区域淋巴结转移、浸润深度、临床分期等呈正相关,TIMP-4的表达与上述临床病理参数呈负相关;MMP-2与TIMP-4在ESCC中的表达呈负相关关系.结论 MMP-2和TIMP-4平衡的破坏是ESCC发生侵袭、转移甚至影响预后的重要因素.