核苷酸切除修复交叉互补基因1核苷酸还原酶M1亚单位和乳腺癌易感基因1mRNA表达与中晚期胃肠道恶性肿瘤化疗方案选择及疗效的关系

目的检测以铂类为基础联合化疗的中晚期胃肠道恶性肿瘤患者中核苷酸切除修复交叉互补基因1(ERCC1)、核苷酸还原酶M1亚单位(RRM1)和乳腺癌易感基因1(BRCA1)mRNA的表达,探讨其与化疗疗效及预后的关系。方法采用mRNA定量检测方法,检测21例以铂类为基础联合化疗的中晚期胃肠道恶性肿瘤患者组织标本中ERCC1、RRM1和BRCA1mRNA的表达,并分析表达状况与化疗疗效及预后之间的关系。结果 (1)中晚期胃肠道恶性肿瘤组织中ERCC1、RRM1和BRCA1 mRNA表达与临床分期无关(P>0.05)。(2)ERCC1mRNA低表达患者化疗后总有效率(50.0%)高于ERCCl mRNA高表达患者(9.1%,P<0.05)。(3)RRM1 mRNA低表达患者化疗后总有效率(41.7%)高于RRM1 mRNA高表达患者(0,P<0.05)。(4)BRCA1 mRNA低表达患者化疗后总有效率(69.2%)高于BRCAl mRNA高表达患者(25.0%,P<0.05)。结论 ERCCl、RRM1和BRCA1mRNA表达水平,对中晚期胃肠道恶性肿瘤患者的化疗疗效及预后具有预测价值。     

DNA切除修复交叉互补基因1、乳腺癌易感基因、核苷酸还原酶1与非小细胞肺癌

 阐述了近年来非小细胞肺癌（NSCLC）化疗敏感性与DNA 切除修复交叉互补基因1 （ERCC1）、乳腺癌易感基因（BRCA1）、核苷酸还原酶1（RRM1）基因表达关系的研究进展，分析3个基因对NSCLC个体化化疗潜在的指导意义     

切除修复交叉互补基因1、乳腺癌易感基因1及微管蛋白β3检测在晚期肺鳞状细胞癌患者GP方案治疗中的指导意义

目的 探讨切除修复交叉互补基因1(ERCC1)、乳腺癌易感基因1(BRCA1)及微管蛋白β3(TUBB3)检测在晚期肺鳞状细胞癌患者吉西他滨+顺铂（GP）方案治疗中的指导意义。方法 选取74例行GP方案治疗的晚期肺鳞状细胞癌患者,采用免疫组化法检测ERCC1、BRCA1及TUBB3表达情况。比较不同临床特征晚期肺鳞状细胞癌患者的ERCC1、BRCA1及TUBB3表达情况。根据免疫组化结果对患者进行分组,3阳性为A组（n=16）,2阳性+1阴性为B组（n=18）,1阳性+2阴性为C组（n=19）,3阴性为D组（n=21）,比较4组患者的临床特征、总有效率及疾病控制率。结果 74例晚期肺鳞状细胞癌患者肺鳞状细胞癌组织中ERCC1、BRCA1、TUBB3阳性表达率分别为45.95%、55.41%、47.30%。不同性别、临床分期、分化程度肺鳞状细胞癌患者肺鳞状细胞癌组织中ERCC1、BRCA1及TUBB3阳性表达率比较,差异均有统计学意义（P﹤0.05）。4组患者的性别、年龄、吸烟时间比较,差异均无统计学意义（P﹥0.05）;4组患者的临床分期、分化程度比较,差异均有统计学意义（P﹤0.05...     

核苷酸切除修复交叉互补基因1 mRNA表达与非小细胞肺癌铂类化疗患者预后的相关性

目的 探讨核苷酸切除修复交叉互补基因1(ERCC1)mRNA表达与非小细胞肺癌(NSCLC)铂类化疗患者临床病理特征的关系及其预后意义.方法 采用实时荧光定量逆转录聚合酶链反应(RT-PCR)方法,检测NSCLC石蜡包埋组织中ERCC1 mRNA的表达水平,并比较其表达水平与NSCLC铂类化疗患者临床病理特征和生存时间之间的关系.结果 61例NSCLC患者中,ERCC1 mRNA的中位表达量为0.48.ERCC1 mRNA表达与NSCLC患者临床病理特征无关.ERCC1mRNA低表达(<0.35)患者经铂类药物化疗后的无进展生存时间为14.3个月,而高表达者为8.0个月,差异有统计学意义(P=0.028).ERCC1 mRNA低表达(<0.28)患者的总生存时间为28.4个月,而高表达者为12.9个月,差异有统计学意义(P=0.0064).Cox多因素回归分析显示,ERCC1 mRNA表达水平是影响NSCLC患者预后的独立因素.结论 ERCC1 mRNA的表达水平可以作为以铂类为基础药物化疗的NSCLC患者预后的独立预测因素,ERCC1 mRNA低表达的NSCLC患者经铂类化疗后,总生存时间明显延长,为制定NSCLC个体化的化疗方案提供了重要信息.     

非小细胞肺癌表皮生长因子受体基因拷贝数与核苷酸切除修复交叉互补基因1和乳腺癌易感基因1的表达及其相关性分析

目的 探讨表皮生长因子受体(EGFR)基因拷贝数与铂类耐药相关基因核苷酸切除修复交叉互补基因1(ERCC1)和乳腺癌易感基因1(BRCA1)在非小细胞肺癌(NSCLC)中的表达情况,以及三者之间的相关性.方法 用荧光原位杂交(FISH)技术检测EGFR基因的扩增情况,应用免疫组化SP法检测132例NSCLC患者标本ERCC1和BRCA1蛋白的表达,并进一步分析EGFR基因拷贝数、ERCC1和BRCA1的蛋白表达与患者临床病理特征的关系.结果 EGFR基因FISH阳性率为24.1% (40/166).女性的扩增阳性率高于男性(31.9%和18.6%,P=0.048);无吸烟史的患者扩增阳性率明显高于有吸烟史的患者(32.8%和16.7%,P=0.045);基因拷贝数增加与患者的年龄、临床分期、病理类型及有无淋巴结或远处转移均无关.ERCC1蛋白表达阳性率为45.5% (60/132),在不同的病理类型分布比较,差异有统计学意义(P=0.046),与患者的性别、年龄、临床分期、有无淋巴结或远处转移及吸烟状况均无关.BRCA1蛋白表达阳性率为35.1%(46/131),与患者的性别、年龄、临床分期、病理类型、淋巴结或远处转移及吸烟状况无关.ERCC1与BRCA1的蛋白表达呈中等相关(r=0.449,P＜0.001),与EGFR扩增无相关性(P=0.785);BRCA1表达与EGFR基因拷贝数状态无相关性(P=0.143).结论 在肺癌的个体化治疗中,检测EGFR基因拷贝数、ERCC1和BRCA1的表达对靶向治疗和铂类药物化疗的选择具有重要的临床指导意义.

Abstract：

Objective To evaluate the expression of epidermal growth factor receptor (EGFR) gene copy number and the expression of ERCC1 and BRCA1 proteins in patients with non-small-cell lung cancer (NSCLC) and the correlation between them. Methods The status of EGFR gene copy number was determined by in situ hybridization (FISH), and the expression of ERCC1 and BRCC1 proteins was examined by immunohistochemistry (IHC). The relationship of EGFR gene copy number with the expression of ERCC1 and BRCA1 and the clinical pathologic features were analyzed. Results FISH-positive EGFR expression was identified in 40 of 166 samples (24.1%). More FISH-positive EGFR in the female than male patients (31.9% vs. 18.6%, P=0.048), and non-smoker than smoker (32.8% vs. 16.7%, P=0.045). FISH-positive EGFR was not associated with age, pathological type, clinical stage and metestasis status (P＞0.05). The expression of ERCC1 protein was identified in 60 of 132 samples (45.5%). The expression of ERCC1 protein varied significantly in tumors of different pathological types (P=0.046), but not associated with age, gender, clinical stage, metestatic status and smoking status (P＞0.05). The expression of BRCA1 protein was identified in 46 of 131 samples (35.1%). The expression of BRCA1 was not associated with age gender, pathological type, clinical stage, metestatic ststus and smoking status (P＞0.05). There was a moderate correlation between the expressions of ERCC1 and BRCA1 (r=0.449, P＜0.001), but EGFR gene copy number was not correlated with the expression of ERCC1 or BRCA1 protein. Conclusions FISH-positive EGFR expression is associated with gender and smoking status, but not correlated with the expression of ERCC1 and BRCA1 proteins. There is a moderate correlation between the expressions of ERCC1 and BRCA1.     

切除修复交叉互补基因1在乳腺癌中的表达及意义

目的 探讨切除修复交叉互补基因1（ERCC1）在乳腺癌组织中的表达与临床病理特征及预后的关系。方法 应用实时荧光定量PCR技术检测363例乳腺癌组织中ERCC1 mRNA的相对表达水平,分析其表达与乳腺癌临床病理特征及预后之间的关系。结果 363例乳腺癌组织标本中ERCC1 mRNA的中位表达水平为1.02×10-2,其中ERCC1 mRNA高表达者181例,ERCC1 mRNA低表达者182例。 ERCC1 mRNA表达水平与ER、PR表达有关（P＜0.05）,而与患者的年龄、肿瘤大小、腋窝淋巴结转移、病理类型、组织学分级、HER-2的表达均无关（P＞0.05）。ERCC1 mRNA高表达与低表达者的中位无病生存期（DFS）均为未达到,差异无统计学意义（P＞0.05）。ERCC1 mRNA高表达者的中位无进展生存期（PFS）为34.0个月（95%CI：32.004～35.996个月）,低表达者的中位PFS为未达到,两组差异有统计学意义（P=0.017）。结论 乳腺癌中ERCC1 mRNA的表达可能与患者的雌激素代谢相关,检测ERCC1 mRNA的表达水平可能有助于判断乳腺癌患者的生存和预后。     

乳腺癌易感基因1和微管蛋白β3在胃癌中的表达及其临床意义

目的:探讨胃癌患者乳腺癌易感基因1（BRCA1）和微管蛋白β3（TUBB3）的表达及其临床意义,为胃癌的精确诊治提供依据。方法:收集2018年12月至2020年5月在安徽省马鞍山市人民医院住院治疗并且接受胃镜活组织检查或手术的46例胃癌患者资料。采用免疫组织化学法检测胃癌组织和癌旁组织中BRCA1和TUBB3蛋白的表达...     

卵巢上皮癌组织MyD88和β-Ⅲ微管蛋白表达生物学意义分析

目的:探讨髓样分化因子88(MyD88)和β-Ⅲ微管蛋白(β-tubulinⅢ)在卵巢上皮癌组织中的表达及其与临床病理参数的关系。方法:采用免疫组织化学SP法检测50例卵巢上皮癌(化疗敏感组和耐药组各25例)和15例正常卵巢组织中MyD88和β-Ⅲ微管蛋白的表达。结果:50例卵巢癌组织中MyD88和β-Ⅲ微管蛋白的阳性表达率分别为36.0%和60.0%,明显高于正常对照组的0和13.3%,差异有统计学意义,P<0.05。MyD88和β-Ⅲ微管蛋白在耐药组中的阳性率分别为52.0%和80.0%,明显高于敏感组的20.0%和40.0%,差异有统计学意义,P<0.05。MyD88与组织分化程度和FIGO分期有关,r分别为-0.302和-0.330,P<0.05。β-Ⅲ微管蛋白与组织分化程度及有无淋巴结转移有关,r分别为-0.323和0.323,P<0.05。MyD88和β-Ⅲ微管蛋白表达呈正相关性,r=0.357,P<0.05。结论:MyD88和β-Ⅲ微管蛋白与卵巢上皮癌化疗耐药密切相关,可预测卵巢上皮癌患者的化疗敏感性。     

核苷酸切除修复交叉互补基因1与卵巢癌顺铂耐药的关系

目的 探讨核苷酸切除修复交叉互补基因1(ERCC1)与卵巢癌顺铂(DDP)耐药的关系.方法 分别应用免疫组化、逆转录聚合酶链反应(RT-PCR)和Western blot检测58例卵巢癌组织和ES-2、SKOV3、COC1、COC1/DDP 4株卵巢癌细胞系中ERCC1基因的表达,分析该基因与DDP化疗耐药的关系,并观察应用RNA干扰技术干扰了ERCC1基因后卵巢癌细胞对DDP敏感性的变化.结果 58例卵巢癌组织中,ERCC1表达阳性者22例,阳性率为37.9%.ERCC1的表达与DDP化疗敏感性有关(P＜0.05),DDP耐药者ERCC1表达的阳性率(57.89%)显著高于敏感者(28.21%,P=0.029).ES-2、SKOV3、COC1、COC1/DDP 4株卵巢癌细胞ERCC1基因的表达与DDP IC50正相关(r=0.932,P＜0.05).RNA干扰ERCC1基因后,ES-2、SKOV3、COC1/DDP细胞对DDP的敏感性分别增加了53.88、5.07、3.75倍.结论 ERCC1基因与卵巢癌DDP耐药有关,RNA干扰ERCC1基因可增强卵巢癌细胞对DDP的敏感性.     

DNA切除修复交叉互补基因1蛋白的表达与鼻咽癌同步放化疗疗效的关系

 目的　研究DNA切除修复交叉互补基因1（ERCC1）在鼻咽癌中的表达,分析其与鼻咽癌同步放化疗疗效的关系。方法　对鼻咽部肿物活组织检查确诊为非分化型非角化性鼻咽癌患者,接受顺铂（DDP）单药同步放化疗,应用免疫组织化学法检测鼻咽部癌组织中ERCC1蛋白表达。患者同步放化疗结束后8周复查鼻咽部磁共振成像（MRI）以评价其近期治疗敏感性,完全缓解（CR）+部分缓解（PR）评价为治疗敏感组,稳定（SD）+进展（PD）评价为治疗不敏感组,以后每3个月复查1次鼻咽部MRI了解有无复发,随访观察3年疗效。分析ERCC1蛋白表达与同步放化疗近期治疗敏感性及远期生存率的关系。结果　全组76例患者均可评价近期治疗敏感性,72例可评价无疾病进展生存时间及总生存（OS）率。可评价近期治疗敏感性的76例患者中CR为56例（73.68 %）,PR 11 例（14.47 %）,SD 3 例（3.95 %）,PD 6 例（7.89 %）;有效率（RR）88.16 %（67／76）,疾病控制率（DCR）92.1 %（70／76）。ERCC1阳性率42.1 %（32／76）,其中治疗敏感组中阳性率37.3 %（24／67）,不敏感组中阳性率 88.8 %（8 ／9）。ERCC1阴性表达组中有效率（RR）97.7 %（43／44）,DCR 97.7 %（43／44）,ERCC1阳性表达组 RR 75 %（24／32）,DCR 81.3 %（26／32）。ERCC1阴性组的治疗有效率显著高于ERCC1阳性组,其差异有统计学意义（χ2＝7.119,P＜0.05）。72例患者12个月无疾病进展率为91.7 %（66／72）。其中ERCC1阴性组95.5 %（39／41）,ERCC1阳性组87.1 %（27／31）,两组间无疾病进展率的差异无统计学意义（χ2＝0.623,P＝0.430）。31例ERCC1阳性患者的1、2、3年生存率分别为90.6 %（28／31）、77.4 %（27／31）、61.3 %（19／31）。41例ERCC1阴性患者的1、2、3年生存率分别为95.5 %（39／41）、90.2 %（37／41）、82.9 %（34／41）。两组间生存率的差异有统计学意义（χ2＝4.192,P＝0.041）。结论　鼻咽癌中ERCC1蛋白的表达与同步放化疗近期治疗敏感性呈负相关性,ERCC1的表达可能预测NPC同步放化疗近期治疗敏感性。鼻咽癌的ERCC1蛋白的表达与 OS 呈负相关性,其可能作为判断NPC预后的一项指标。     

非小细胞肺癌组织中DNA切除修复交叉互补基因1mRNA的表达及其对预后的影响

Objective To investigate the level of ERCC1 mRNA expression in non-small cell lung cancer and analyze the influencing factors of the survival of patients after operation. Methods The level of ERCC1 mRNA expression was quantified in sixty pairs of non-small cell lung cancer tissue and their matched normal lung tissues by real-time PCR assay. The survival of patients was analyzed by univariate Kaplan-Meier and Cox regression analysis. Results The level of ERCC1 mRNA expression in cancer tissues ( -7.85 ±3.86) was significantly higher than that in matched normal ones ( - 11. 19 ±5.03;t=3.973, P=0.000). Up-regulation of ERCC1 mRNA was found in 43 of 60 (71.7% ) lung cancer tissues compared with that in the matched normal lung tissues (17 of 60, 28.3% ). The univariate survival analysis by Kaplan-Meier method showed that the survival rate of patients with high ERCC1 mRNA expression was lower than that in the patients with low expression of ERCC1 mRNA (P=0.000). Patients with lymph node metastasis, smoking, cancer family history, or high pathological grade had significantly shorter survaival time than those without lymph node metastasis, smoking, cancer family history, or with low pathological grade. Cox regression survival analysis showed that the level of ERCC1 mRNA expression, lymph node metastasis, smoking, and pathological grade were significant independent factors affecting the survival rate. Conclusions Non-small cell lung cancer patients with up-regulated ERCC1 expression have a poor survival. The expression of ERCC1 mRNA, lymph node metastasis, pathological grade, cancer family history and smoking can be used as prognostic indicator of non-small cell lung cancer.     

非小细胞肺癌组织中DNA切除修复交叉互补基因1mRNA的表达及其对预后的影响

目的 探讨非小细胞肺癌(NSCLC)组织中DNA切除修复交叉互补基因1(ERCC1)的表达水平,及其对NSCLC患者预后的影响.方法 采用实时定量PCR技术检测60例NSCLC患者的癌组织及癌旁正常组织中ERCCI mRNA表达水平,采用Kaplan-Meier单因素与Cox多元回归进行生存分析.结果 NSCLC患者癌组织和癌旁相应正常组织中ERCCI mRNA的表达水平分别为-7.85 4±3.86和-11.194±5.03,差异有统计学意义(t=3.973,P=0.000).60例NSCLC中,ERCCI mRNA 高表达43例(71.6%),低表达17例(28.3%).Kaplan-Meier法生存分析显示,ERCCI mRNA高表达患者的生存率显著低于低表达患者(P=0.0003),淋巴结转移患者的生存率低于无淋巴结转移患者(P=0.026),有肿瘤家族史患者的生存率低于无肿瘤家族史患者(P=0.049),病理分级高的患者生存率低于病理分级低的患者(P=0.031).Cox回归分析结果显示,ERCCI mRNA表达水平、有无淋巴结转移、病理分级和是否吸烟是影响NSCLC患者术后生存的独立危险因素.结论 NSCLC组织中ERCCI高表达的患者术后生存时间较短.ERCCI mRNA表达水平、有无淋巴结转移、病理分级、肿瘤家族史和是否吸烟可作为评价NSCLC患者预后的参考指标.

Abstract：

Objective To investigate the level of ERCC1 mRNA expression in non-small cell lung cancer and analyze the influencing factors of the survival of patients after operation. Methods The level of ERCC1 mRNA expression was quantified in sixty pairs of non-small cell lung cancer tissue and their matched normal lung tissues by real-time PCR assay. The survival of patients was analyzed by univariate Kaplan-Meier and Cox regression analysis. Results The level of ERCC1 mRNA expression in cancer tissues ( -7.85 ±3.86) was significantly higher than that in matched normal ones ( - 11. 19 ±5.03;t=3.973, P=0.000). Up-regulation of ERCC1 mRNA was found in 43 of 60 (71.7% ) lung cancer tissues compared with that in the matched normal lung tissues (17 of 60, 28.3% ). The univariate survival analysis by Kaplan-Meier method showed that the survival rate of patients with high ERCC1 mRNA expression was lower than that in the patients with low expression of ERCC1 mRNA (P=0.000). Patients with lymph node metastasis, smoking, cancer family history, or high pathological grade had significantly shorter survaival time than those without lymph node metastasis, smoking, cancer family history, or with low pathological grade. Cox regression survival analysis showed that the level of ERCC1 mRNA expression, lymph node metastasis, smoking, and pathological grade were significant independent factors affecting the survival rate. Conclusions Non-small cell lung cancer patients with up-regulated ERCC1 expression have a poor survival. The expression of ERCC1 mRNA, lymph node metastasis, pathological grade, cancer family history and smoking can be used as prognostic indicator of non-small cell lung cancer.     

非小细胞肺癌组织中DNA切除修复交叉互补基因1mRNA的表达及其对预后的影响

Objective To investigate the level of ERCC1 mRNA expression in non-small cell lung cancer and analyze the influencing factors of the survival of patients after operation. Methods The level of ERCC1 mRNA expression was quantified in sixty pairs of non-small cell lung cancer tissue and their matched normal lung tissues by real-time PCR assay. The survival of patients was analyzed by univariate Kaplan-Meier and Cox regression analysis. Results The level of ERCC1 mRNA expression in cancer tissues ( -7.85 ±3.86) was significantly higher than that in matched normal ones ( - 11. 19 ±5.03;t=3.973, P=0.000). Up-regulation of ERCC1 mRNA was found in 43 of 60 (71.7% ) lung cancer tissues compared with that in the matched normal lung tissues (17 of 60, 28.3% ). The univariate survival analysis by Kaplan-Meier method showed that the survival rate of patients with high ERCC1 mRNA expression was lower than that in the patients with low expression of ERCC1 mRNA (P=0.000). Patients with lymph node metastasis, smoking, cancer family history, or high pathological grade had significantly shorter survaival time than those without lymph node metastasis, smoking, cancer family history, or with low pathological grade. Cox regression survival analysis showed that the level of ERCC1 mRNA expression, lymph node metastasis, smoking, and pathological grade were significant independent factors affecting the survival rate. Conclusions Non-small cell lung cancer patients with up-regulated ERCC1 expression have a poor survival. The expression of ERCC1 mRNA, lymph node metastasis, pathological grade, cancer family history and smoking can be used as prognostic indicator of non-small cell lung cancer.     

转移性恶性胸腹腔积液患者肿瘤细胞中乳腺癌易感基因1mRNA的表达与铂类敏感性的关系

目的 研究乳腺癌易感基因1(BRCA1)在转移性恶性胸腹腔积液肿瘤细胞中的表达,并探讨BRCA1基因表达在铂类化疗疗效中的预测作用.方法 收集31例经病理确诊的恶性胸腹腔积液标本,分离原代肿瘤细胞.采用细胞计数试剂盒(CCK8)体外药物敏感性试验,检测顺铂(DDP)对原代肿瘤细胞的抗肿瘤作用,采用实时荧光定量PCR法检测肿瘤细胞中BRCA1 mRNA的相对表达水平.结果 BRCA1 mRNA在原代肿瘤细胞中的表达水平为0.618(0.014～18.063),DDP对原代肿瘤细胞的半数抑制浓度(IC50)为2.809 μg/ml (0.118～19.439 μg/ml).BRCA1 mRNA的表达及DDP对原代肿瘤细胞的IC50值与患者的年龄、性别、原发肿瘤类型、是否接受化疗以及积液类型均无关(均P＞0.05).BRCA1 mRNA的表达水平与DDP抵抗正相关,BRCA1 mRNA低表达者对DDP的敏感性高(r=0.786,P＜0.001).结论 检测BRCA1 mRNA的表达水平可以为转移性胸腹腔积液患者应用铂类药物化疗提供理论依据.

Abstract：

Objective To explore the mRNA expression of breast cancer susceptibility gene 1 (BRCA1) in tumor cells isolated from malignant pleural and peritoneal effusions, and the predictive role of BRCA1 related to the efficacy of cisplatin-based chemotherapy. Methods Tumor cells were isolated from malignant pleural and peritoneal effusions of 31 cancer patients. The response of these tumor cells to cisplatin was determined by CCK8 assay. Real time quantitative RT-PCR was used to examine the BRCA1 mRNA level in the primary culture cancer cells. Results The expression level of BRCA1 mRNA was 0.618(0.014-18.063)in primary culture tumor cells. The IC50 of DDP was 2.809 μg/ml in the primary culture tumor cells (0.118-19.439 μg/ml). Both BRCA1 mRNA expression and the tumor cells IC50 of DDP were not significantly related with patient age, gender, the type of primary tumor, whether to accept the chemotherapy and effusion type (P>0.05). The level of BRCA1 mRNA was negatively correlated with the chemosensitivity in terms of IC50 of cisplatin (P<0.001). Conclusion Assessment of expression level of BRCA1 mRNA may be useful in predicting the efficacy of cisplatin-based chemotherapy in patients with metastatic malignant effusions.     

非小细胞肺癌β-ｔｕｂｕｌｉｎⅢ表达与微管蛋白结合类化疗药物敏感性的关系

目的　探讨进展期非小细胞肺癌（ＮＳＣＬＣ）组织β微管蛋白Ⅲ（β-ｔｕｂｕｌｉｎⅢ）的表达情况及其与含微管蛋白结合类化疗药物敏感性之间的关系。方法　收集２００２年１月至２００６年１２月经病理组织学检查确诊的ⅢＢ、Ⅳ期ＮＳＣＬＣ初治患者１２０例,采用免疫组化法检测活检癌组织中β-ｔｕｂｕｌｉｎⅢ的表达。所有患者行４～６个周期异长春花碱或紫杉类联合顺铂化疗,评价治疗有效率（ＲＲ）,随访总生存时间（ＯＳ）和肿瘤进展时间（ＴＴＰ）,分析上述指标以及临床特征与β-ｔｕｂｕｌｉｎⅢ表达之间的关系。结果　５３例患者均可评价疗效。β-ｔｕｂｕｌｉｎⅢ高表达者（ｎ＝３１）的ＲＲ、ＯＳ、ＴＴＰ分别为９．４％、（２７７.２６±１１２.８２）天和（１７０.０６±７１.４５）天,均显著低于β-ｔｕｂｕｌｉｎⅢ低表达者（ｎ＝２２）的４５.５％、（４５７.３２±２０７.１２）天和（２８９.４５±１２９.７８）天（Ｐ＜０.００１）。β-ｔｕｂｕｌｉｎⅢ表达与性别、年龄、病理类型、吸烟情况、ＴＮＭ分期、基础疾病情况、合并症、癌症家族史、ＰＳ评分等临床病理特征均无关。结论　进展期ＮＳＣＬＣ的β-ｔｕｂｕｌｉｎⅢ表达情况可能与接受微管蛋白结合类化疗药物的敏感性有关,低表达者疗效及预后均优于高表达者。β-ｔｕｂｕｌｉｎⅢ表达与临床病理特征无关。     

切除修复交叉互补基因1表达与非小细胞肺癌患者吉西他滨联合顺铂化疗疗效的相关性

目的探讨非小细胞肺癌(NSCLC)患者肿瘤组织内核苷酸切除修复交叉互补基因1(ERCC1)表达与吉西他滨联合顺铂(GP方案)化疗疗效的相关性。方法采用免疫组化S-P法检测51例Ⅱb～Ⅳ期NSCLC患者肿瘤组织内ERCC1的表达。所有患者接受至少2个周期以上的GP方案化疗,对患者化疗后的中位生存期(MST)及化疗后反应率(RR)进行评估。结果 51例患者ERCC1的阳性表达率为43.14%(22/51)。ERCC1表达阳性组化疗后的RR和MST分别为50.0%、17个月,与阴性组RR(31.04%)、MST(12个月)比较,差异无统计学意义(χ2=1.8877,P=0.1695;χ2=1.6767,P=0.1954)。结论 ERCC1表达阳性的NSCLC患者能从吉西他滨联合顺铂的化疗中受益,调控ERCC1表达逆转耐药的策略,将为肿瘤治疗带来新的方法和途径。     

初治与复发性卵巢上皮癌组织中BRCA1、ERCC1、TUBB3、PRR13基因mRNA表达变化

目的 比较BRCA1、ERCC1、TUBB3、PRR13基因mRNA表达在初治和复发性卵巢上皮癌组织中的表达水平的差异,初步探讨该4种耐药相关基因与卵巢癌获得性耐药的关系.方法采用荧光定量PCR方法检测46例原发性卵巢上皮癌和14例复发性卵巢上皮癌组织标本中BRCA1、ERCC1、TUBB3、PRR13基因mRNA表...     

Ⅲ型β-微管蛋白和多药耐药基因1蛋白表达与非小细胞肺癌生物学特性的相关性

目的 探讨Ⅲ型β-微管蛋白(Ⅲβ-tubulin)和多药耐药基因1(MDR1)蛋白在非小细胞肺癌(NSCLC)中的表达特征及临床意义.方法 应用免疫组化法检测158例NSCLC组织中Ⅲβ-tubulin和MDR1蛋白的表达,应用Western blot检测新鲜NSCLC组织及相应癌旁正常组织中Ⅲβ-tubulin和MDR1蛋白的表达,并分析其表达与NSCLC生物学特性的关系.结果 Ⅲβ-tubulin和MDR1蛋白在NSCLC中的阳性表达率分别为65.2%和51.3%.Western blot结果显示,Ⅲβ-tubulin和MDR1蛋白在NSCLC组织中的表达明显高于癌旁正常肺组织(P＜0.01).Ⅲβ-tubulin在中、高分化腺癌中的表达明显低于低分化腺癌(P＜0.01),肺腺癌中MDR1蛋白的表达明显高于鳞癌和大细胞未分化癌(P＜0.01).Ⅲβ-tubulin在Ⅲ～Ⅳ期NSCLC中的表达高于Ⅰ～Ⅱ期(P＜0.05),而MDR1蛋白的表达差异无统计学意义(P＞0.05).Ⅲβ-tubulin和MDR1蛋白阳性表达与患者年龄、性别、肿瘤大小及淋巴结状态无明显相关性(P＞0.05).结论 Ⅲβ-tubulin和MDR1蛋白在NSCLC的发生、发展中有一定作用,可作为判断NSCLC预后的重要指标.     

晚期非小细胞肺癌组织中切除修复交叉互补基因1和核糖核苷酸还原酶亚单位1表达与吉西他滨联合顺铂治疗的相关性研究

目的探讨核苷酸切除修复交叉互补基因1(ERCC1)和核糖核苷酸还原酶(RR)亚单位M1(RRM1)在Ⅳ期非小细胞肺癌(NSCLC))组织中的表达水平,分析其与吉西他滨联合顺铂(GP)方案化疗疗效的关系。方法采用液相芯片技术检测148例经过4个周期以上GP方案化疗的Ⅳ期NSCLC组织中RRM1和ERCC1的表达情况。结果Ⅳ期NSCLC组织中ERCC1的阳性率为47.3%,RRM1的阳性率为35.1%,与患者的性别、年龄及是否吸烟无关。ERCC1和RRM1低表达者接受GP方案化疗的效果均优于高表达者,两者差异有统计学意义(P<0.05)。此外,RRM1低表达的患者生存时间明显长于高表达者(P=0.004)。结论晚期NSCLC患者组织中ERCC1和RRM1mRNA的表达与GP方案化疗疗效及预后密切相关。     

人表皮生长因子受体2切除修复交叉互补基因1表皮生长因子受体表达和表皮生长因子受体基因扩增对食管鳞癌含铂方案化疗疗效的预测价值

目的探讨人表皮生长因子受体2(HER2)、切除修复交叉互补基因1(ERCC1)、表皮生长因子受体(EGFR)的表达以及EGFR基因扩增能否预测含铂方案治疗晚期食管鳞癌的疗效。方法回顾性分析57例采用含铂方案进行一线化疗的晚期食管鳞癌患者,应用免疫组化的方法检测HER2、ERCC1和EGFR的表达,并在EGFR表达为弱阳性(++)和强阳性(+++)的患者中(24例)应用荧光原位杂交(FISH)技术检测EGFR基因扩增。结果 HER2、ERCC1和EGFR的表达率分别为15.8%、47.4%和55.3%,24例EGFR(++)和(+++)的患者中EGFR基因扩增为16.9%,未发现HER2、ERCC1和EGFR的表达与化疗的客观缓解率(ORR)、肿瘤进展时间(TTP)和中位生存时间(OS)相关。EGFR基因扩增患者的OS有缩短的趋势。结论 HER2、ERCC1和EGFR的表达可能不能预测含铂方案治疗晚期食管鳞癌的疗效,需要寻找新的疗效预测指标。