BRCA1、ERCC1、β-tubulinⅢ和RRM1的表达对Ⅱ～Ⅳ期非小细胞肺癌术后化疗药物确定及生存趋势的影响
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摘要
目的研究BRCA1、ERCC1、β-tubulinⅢ和RRM1的表达对Ⅱ～Ⅳ期非小细胞肺癌术后化疗药物的确定以及生存趋势的影响。方法选取2013年6月至2015年7月进行手术治疗的93例非小细胞肺癌患者,采用免疫组化法对93例手术切除同时采取辅助化疗的非小细胞肺癌患者的肿瘤组织进行BRCA1、ERCC1、β-tubulinⅢ和RRM1水平的检测,分析其在患者组织中的表达与相关指标、临床病理等因素的关系,通过随访分析其与患者生存期、2年生存率的相关性,以及与患者不同辅助化疗药物选择的关系。结果本研究患者组织中BRCA1在Ⅱ～Ⅳ期非小细胞肺癌患者肿瘤组织中的表达与统计的临床病理特征无显著差异(P> 0. 05)。ERCC1的阳性表达与患者的淋巴结转移有密切关系(P <0. 05);β-tubulinⅢ在较年轻及鳞癌类型患者中的表达量较高,与年长(> 60岁)及腺癌患者中的表达均有显著差异(P <0. 05); RRM1与统计的临床病理特征无显著的相关性(P> 0. 05)。BRCA1、ERCC1、β-tubulinⅢ及RRM1阳性表达患者平均总生存期(月)均显著短于阴性患者,2年生存率也明显低于阴性患者(P <0. 05)。RRM1与吉西他滨辅助化疗相关(P <0. 05),β-tubulinⅢ与多西他赛和长春瑞滨辅助化疗方案的选择具有一定的相关性(P <0. 05),而BRCA1、ERCC1、RRM1与紫杉醇辅助化疗方案的选择具有一定的相关性(P <0. 05)。结论通过免疫组织化学的方法对BRCA1、ERCC1、β-tubulinⅢ和RRM1的表达水平进行检测,在一定程度上对Ⅱ～Ⅳ期非小细胞肺癌患者的术后辅助化疗药物的选择具有一定的指导作用,并能初步预测患者术后的生存趋势。
Objective To investigate the effects of BRCA1,ERCC1,β-tubulinⅢ,RRM1 effects of BRCA1,ERCC1,β-tubulinⅢ,RRM1 on the determination of chemotherapy drugs and postoperative survival trend in patients with non-small cell lung cancer( NSCLC) at Ⅱ～Ⅳ stage. Methods A total of 93 patients with NSCLC at Ⅱ～Ⅳ stage who were treated in our hospital from June 2013 to July 2015 were enrolled in the study. The levels of BRCA1,ERCC1,β-tubulinⅢ,RRM1 in tumor tissues were detected by using immunohistochemical method to analysis the relationship between the expression levels of the indexes and clinical pathological factors. And the correlation between the expression levels of the indexes and survival time,2-year survival rate of patients was analyzed,Moreover the the correlation between the expression levels of the indexes and the selection of different chemotherapeutics was analyzed. Results There were no significant differences in the expression levels of BRCA1 in tumor tissues and clinical pathological characteristics of patients with NSCLC at Ⅱ～Ⅳ stage( P > 0. 05). The positive expression of ERCC1 was closely correlated with lymph node metastasis of patients( P < 0. 05). Moreover the expression levels of β-tubulinⅢ in younger patients and the patients with squamous cell carcinoma adenocarcinoma were higher( P < 0. 05),there were significant differences in the expression levels between younger patients as well as the patients with squamous cell carcinoma and the older patients as well as the patients with adenocarcinoma( P < 0. 05). However there were no significant differences between the expression levels of RRM1 and clinical pathological characteristics( P > 0. 05).Moreover the total survival duration( month) and 2-year survival rate in patients with positive expressions of BRCA1,ERCC1,β-tubulinⅢ and RRM1 were significantly less than those of patients with negative expressions of BRCA1,ERCC1,β-tubulinⅢ( P < 0. 05). In addition RRM1 was associated with gemcitabine chemotherapy( P < 0. 05),and β-tubulinⅢ was related with docetaxel and vinorelbine chemotherapy scheme( P < 0. 05),however,BRCA1,ERCC1 and RRM1 were correlated with paclitaxel adjuvant chemotherapy( P < 0. 05). Conclusion The detection of expression levels of BRCA1,ERCC1,β-tubulinⅢ and RRM1 by immunohistochemical method can direct the chemotherapeutics selection and can forecast the postoperative survival trend of patients with NSCLC after operation.
Objective To investigate the effects of BRCA1,ERCC1,β-tubulinⅢ,RRM1 effects of BRCA1,ERCC1,β-tubulinⅢ,RRM1 on the determination of chemotherapy drugs and postoperative survival trend in patients with non-small cell lung cancer( NSCLC) at Ⅱ～Ⅳ stage. Methods A total of 93 patients with NSCLC at Ⅱ～Ⅳ stage who were treated in our hospital from June 2013 to July 2015 were enrolled in the study. The levels of BRCA1,ERCC1,β-tubulinⅢ,RRM1 in tumor tissues were detected by using immunohistochemical method to analysis the relationship between the expression levels of the indexes and clinical pathological factors. And the correlation between the expression levels of the indexes and survival time,2-year survival rate of patients was analyzed,Moreover the the correlation between the expression levels of the indexes and the selection of different chemotherapeutics was analyzed. Results There were no significant differences in the expression levels of BRCA1 in tumor tissues and clinical pathological characteristics of patients with NSCLC at Ⅱ～Ⅳ stage( P > 0. 05). The positive expression of ERCC1 was closely correlated with lymph node metastasis of patients( P < 0. 05). Moreover the expression levels of β-tubulinⅢ in younger patients and the patients with squamous cell carcinoma adenocarcinoma were higher( P < 0. 05),there were significant differences in the expression levels between younger patients as well as the patients with squamous cell carcinoma and the older patients as well as the patients with adenocarcinoma( P < 0. 05). However there were no significant differences between the expression levels of RRM1 and clinical pathological characteristics( P > 0. 05).Moreover the total survival duration( month) and 2-year survival rate in patients with positive expressions of BRCA1,ERCC1,β-tubulinⅢ and RRM1 were significantly less than those of patients with negative expressions of BRCA1,ERCC1,β-tubulinⅢ( P < 0. 05). In addition RRM1 was associated with gemcitabine chemotherapy( P < 0. 05),and β-tubulinⅢ was related with docetaxel and vinorelbine chemotherapy scheme( P < 0. 05),however,BRCA1,ERCC1 and RRM1 were correlated with paclitaxel adjuvant chemotherapy( P < 0. 05). Conclusion The detection of expression levels of BRCA1,ERCC1,β-tubulinⅢ and RRM1 by immunohistochemical method can direct the chemotherapeutics selection and can forecast the postoperative survival trend of patients with NSCLC after operation.
引文
1张连美,仲纪祥,孙苏安. EGFR、ALK和Ki-67在非小细胞肺癌中的表达及相关性分析.临床肺科杂志,2017,22:4-7.
2 罗承逊,陈易华.非小细胞肺癌的靶点及靶向治疗药物的应用.西南军医,2017,19:63-65.
3 但卫斌,黄小芳,吴大和,等. 60例非小细胞肺癌中IL-21R、MMP-2的表达及意义.肿瘤学杂志,2017,23:5.
4 产翠翠,田静,金艺凤.非小细胞肺癌靶向治疗药物的研究进展.中国临床药理学与治疗学,2016,21:354-360.
5 赵铎,高宝安.中晚期非小细胞肺癌联合治疗研究进展.海南医学,2016,27:438-441.
6 Torigoe H,Soh J,Tomida S,et al. Induction chemoradiotherapy using docetaxel and cisplatin with definitive-dose radiation followed by surgery for locally advanced non-small cell lung cancer. J Thorac Dis,2017,9:3076-3086.
7 Chen X,Xie C,Fan XX,et al. Novel direct AMPK activator suppresses non-small cell lung cancer through inhibition of lipid metabolism.Oncotarge,2017,8:96089-96102.
8 Hawkins PG,Boonstra PS,Hobson ST,et al. Prediction of radiation esophagitis in non-small cell lung cancer using clinical factors,dosimetric parameters,and pretreatment cytokine levels. Transl Oncol,2017,11:102-108.
9 Becker M,Ryan L,Dowiak A,et al. A molecular and cytogenetic update on non-small cell lung carcinoma. J Assoc Genet Technol,2017,43:199-211.
10 Kaur H,Sehgal IS,Bal A,et al. Evolving epidemiology of lung cancer in India:Reducing non-small cell lung cancer-not otherwise specified and quantifying tobacco smoke exposure are the key. Indian J Cancer,2017,54:285-290.
11 Prabhu VV,Devaraj N. Epidermal growth factor receptor tyrosine kinase:a potential target in treatment of non-small-cell lung carcinoma.J Environ Pathol Toxicol Oncol,2017,36:151-158.
12 Sepesi B,Cuentas EP,Canales JR,et al. Programmed death cell ligand 1(PD-L1)is associated with survival in stageⅠnon-small cell lung cancer. Semin Thorac Cardiovasc Surg,2017,29:408-415.
13 张春节,姜维美,韩磊,等.晚期非小细胞肺癌中ERCC1、β-tubulin3及TOPOⅡ的表达与临床病理特征及铂类化疗疗效的关系.中国当代医药,2016,23:7-10.
14 Guo ZP,Hu YC,Xie Y,et al. ml N4924 suppresses the BRCA1 complex and synergizes with PARP inhibition in NSCLC cells. Biochem Biophys Res Commun,2017,483:223-229.
15 Karanam NK,Srinivasan K,Ding L,et al. Tumor-treating fields elicit a conditional vulnerability to ionizing radiation via the downregulation of BRCA1 signaling and reduced DNA double-strand break repair capacity in non-small cell lung cancer cell lines. Cell Death Dis,2017,8:e2711.
16 Wang S,Liu F,Zhu J,et al. DNA repair genes ERCC1 and BRCA1expression in non-small cell lung cancer chemotherapy drug resistance.Med Sci Monit,2016,12:999-2005.
17 Lafuente-Sanchis A,Zú1iga,Galbis JM,et al. Prognostic value of ERCC1,RRM1,BRCA1 and SETDB1 in early stage of non-small cell lung cancer. Clin Transl Oncol,2016,18:798-804.
18 Tao H,Zhang Y,Li Q,et al. Methodological quality evaluation of systematic reviews or meta-analyses on ERCC1 in non-small cell lung cancer:a systematic review. J Cancer Res Clin Oncol,2017,143:2245-2256.
19 Wei B,Wang J,Zhang X,et al. Combination of histoculture drug response assay and qPCR as an effective method to screen biomarkers for personalized chemotherapy in esophageal cancer. Oncol Lett,2017,14:6915-6922.
20 Liu J,Zhang L,Mao P,et al. Functional characterization of a novel transcript of ERCC1 in chemotherapy resistance of ovarian cancer.Oncotarget,2017,8:85759-85771.
21 石俊忠,庄建彬,张传山,等.β-tubulinⅢ在结肠腺癌组织中的表达及其临床意义.吉林大学学报,2017,43:770-775.
22 徐辉,邓首军,李振华,等.β-tubulinⅢ在非小细胞肺癌中的研究进展.中国肿瘤外科杂志,2017,9:129-131.
23 张春节,姜维美,韩磊,等. ERCC1、β-tubulin3在非小细胞肺癌中的免疫组织化学及相关基因表达的差异.中国医药指南,2017,15:109-110.
24 张强,翟西菊,魏丽,等.非小细胞肺癌化疗药物耐药性及其与ERCC1、RRM1表达的相关性.实用医药杂志,2017,34:11-13,19.
25 朱伟,叶雷. RRM1蛋白在NSCLC组织中的表达及其临床意义.贵州医药,2017,41:684-686.
2 罗承逊,陈易华.非小细胞肺癌的靶点及靶向治疗药物的应用.西南军医,2017,19:63-65.
3 但卫斌,黄小芳,吴大和,等. 60例非小细胞肺癌中IL-21R、MMP-2的表达及意义.肿瘤学杂志,2017,23:5.
4 产翠翠,田静,金艺凤.非小细胞肺癌靶向治疗药物的研究进展.中国临床药理学与治疗学,2016,21:354-360.
5 赵铎,高宝安.中晚期非小细胞肺癌联合治疗研究进展.海南医学,2016,27:438-441.
6 Torigoe H,Soh J,Tomida S,et al. Induction chemoradiotherapy using docetaxel and cisplatin with definitive-dose radiation followed by surgery for locally advanced non-small cell lung cancer. J Thorac Dis,2017,9:3076-3086.
7 Chen X,Xie C,Fan XX,et al. Novel direct AMPK activator suppresses non-small cell lung cancer through inhibition of lipid metabolism.Oncotarge,2017,8:96089-96102.
8 Hawkins PG,Boonstra PS,Hobson ST,et al. Prediction of radiation esophagitis in non-small cell lung cancer using clinical factors,dosimetric parameters,and pretreatment cytokine levels. Transl Oncol,2017,11:102-108.
9 Becker M,Ryan L,Dowiak A,et al. A molecular and cytogenetic update on non-small cell lung carcinoma. J Assoc Genet Technol,2017,43:199-211.
10 Kaur H,Sehgal IS,Bal A,et al. Evolving epidemiology of lung cancer in India:Reducing non-small cell lung cancer-not otherwise specified and quantifying tobacco smoke exposure are the key. Indian J Cancer,2017,54:285-290.
11 Prabhu VV,Devaraj N. Epidermal growth factor receptor tyrosine kinase:a potential target in treatment of non-small-cell lung carcinoma.J Environ Pathol Toxicol Oncol,2017,36:151-158.
12 Sepesi B,Cuentas EP,Canales JR,et al. Programmed death cell ligand 1(PD-L1)is associated with survival in stageⅠnon-small cell lung cancer. Semin Thorac Cardiovasc Surg,2017,29:408-415.
13 张春节,姜维美,韩磊,等.晚期非小细胞肺癌中ERCC1、β-tubulin3及TOPOⅡ的表达与临床病理特征及铂类化疗疗效的关系.中国当代医药,2016,23:7-10.
14 Guo ZP,Hu YC,Xie Y,et al. ml N4924 suppresses the BRCA1 complex and synergizes with PARP inhibition in NSCLC cells. Biochem Biophys Res Commun,2017,483:223-229.
15 Karanam NK,Srinivasan K,Ding L,et al. Tumor-treating fields elicit a conditional vulnerability to ionizing radiation via the downregulation of BRCA1 signaling and reduced DNA double-strand break repair capacity in non-small cell lung cancer cell lines. Cell Death Dis,2017,8:e2711.
16 Wang S,Liu F,Zhu J,et al. DNA repair genes ERCC1 and BRCA1expression in non-small cell lung cancer chemotherapy drug resistance.Med Sci Monit,2016,12:999-2005.
17 Lafuente-Sanchis A,Zú1iga,Galbis JM,et al. Prognostic value of ERCC1,RRM1,BRCA1 and SETDB1 in early stage of non-small cell lung cancer. Clin Transl Oncol,2016,18:798-804.
18 Tao H,Zhang Y,Li Q,et al. Methodological quality evaluation of systematic reviews or meta-analyses on ERCC1 in non-small cell lung cancer:a systematic review. J Cancer Res Clin Oncol,2017,143:2245-2256.
19 Wei B,Wang J,Zhang X,et al. Combination of histoculture drug response assay and qPCR as an effective method to screen biomarkers for personalized chemotherapy in esophageal cancer. Oncol Lett,2017,14:6915-6922.
20 Liu J,Zhang L,Mao P,et al. Functional characterization of a novel transcript of ERCC1 in chemotherapy resistance of ovarian cancer.Oncotarget,2017,8:85759-85771.
21 石俊忠,庄建彬,张传山,等.β-tubulinⅢ在结肠腺癌组织中的表达及其临床意义.吉林大学学报,2017,43:770-775.
22 徐辉,邓首军,李振华,等.β-tubulinⅢ在非小细胞肺癌中的研究进展.中国肿瘤外科杂志,2017,9:129-131.
23 张春节,姜维美,韩磊,等. ERCC1、β-tubulin3在非小细胞肺癌中的免疫组织化学及相关基因表达的差异.中国医药指南,2017,15:109-110.
24 张强,翟西菊,魏丽,等.非小细胞肺癌化疗药物耐药性及其与ERCC1、RRM1表达的相关性.实用医药杂志,2017,34:11-13,19.
25 朱伟,叶雷. RRM1蛋白在NSCLC组织中的表达及其临床意义.贵州医药,2017,41:684-686.