摘要
目的研究非小细胞肺癌组织中脯氨酰羟化酶3(PHD3)与低氧诱导因子1α(HIF-1α)的表达及关系,并探讨其在非小细胞肺癌发病过程中的临床意义。方法收集河北大学附属医院2010年7月—2012年4月手术切除的非小细胞肺癌标本89例,并取非小细胞肺癌组织、癌旁正常肺组织(距离肿瘤边缘>5 cm)标本进行实验。淋巴结转移51例(淋巴结转移组),无淋巴结转移38例(无淋巴结转移组);肿瘤分期(TNM):Ⅰ期26例,Ⅱ期34例,Ⅲ期29例。分别采用反转录聚合酶链反应(RT-PCR)和免疫印迹法(Western blotting)检测PHD3和HIF-1α的mRNA和蛋白表达水平,并分析其相关性。结果 PHD3 mRNA在非小细胞肺癌组织中的相对表达量为(17.8±2.9),高于癌旁正常肺组织中的(7.1±1.3)(t=31.763,P<0.05);PHD3蛋白在非小细胞肺癌组织中的相对表达量为(13.0±2.8),低于癌旁正常肺组织中的(20.7±4.2)(t=14.391,P<0.05)。癌旁正常肺组织及非小细胞肺癌组织不同临床分期PHD3 mRNA及蛋白相对表达量比较,差异有统计学意义(P<0.05);随着TNM分期的增加,PHD3mRNA的相对表达量增高,而PHD3蛋白的相对表达量降低(P<0.05)。癌旁正常肺组织及有无淋巴结转移组PHD3mRNA及蛋白相对表达量比较,差异有统计学意义(P<0.05);且淋巴结转移组PHD3 mRNA的相对表达量高于癌旁正常肺组织和无淋巴结转移组,PHD3蛋白的相对表达量低于癌旁正常肺组织和无淋巴结转移组(P<0.05)。HIF-1αmRNA在非小细胞肺癌组织中的相对表达量为(17.2±2.9),高于癌旁正常肺组织中的(6.5±1.2)(t=32.163,P<0.05);HIF-1α蛋白在非小细胞肺癌组织中的相对表达量为(20.9±3.8),高于癌旁正常肺组织的(9.2±1.8)(t=26.251,P<0.05)。癌旁正常肺组织及非小细胞肺癌组织不同临床分期HIF-1αmRNA及蛋白相对表达量比较,差异有统计学意义(P<0.05);随着TNM分期的增加,HIF-1αmRNA、HIF-1α蛋白的相对表达量增高(P<0.05)。癌旁正常肺组织及有无淋巴结转移组HIF-1αmRNA及蛋白相对表达量比较,差异有统计学意义(P<0.05);且淋巴结转移组HIF-1αmRNA及蛋白的相对表达量高于癌旁正常肺组织和无淋巴结转移组(P<0.05)。非小细胞肺癌组织PHD3蛋白的表达与HIF-1α蛋白的表达呈负相关(r=-0.746,P<0.05);PHD3 mRNA的表达与HIF-1α蛋白表达呈正相关(r=0.792,P<0.05)。结论 PHD3调控HIF-1α表达可能在非小细胞肺癌的发病中发挥了重要作用,为临床将其作为抑制肿瘤发病的新靶点提供了理论依据。
Objective To investigate the dynamic expression of Prolyl Hydroxulase 3（ PHD3） and Hypoxia-inducibla Facctor- 1α（ HIF- 1α） in non- small cell lung cancer（ NSCLC）. And to explore its clinical significance in the pathogenesis of NSCLC. Methods Eighty- nine cases of NSCLC tumor and adjacent normal lung tissue samples were collected from July2010 to April 2012 in Affiliated Hospital of Hebei University. Taking the NSCLC tissue,adjacent normal lung tissue（ from the tumor edge 〉5 cm） specimens were test. 51 cases with lymph node metastasis（ lymph node metastasis group）,38 cases without lymph node metastasis（ without lymph node metastasis group）; tumor staging（ TNM） ： 26 cases of stage Ⅰ,34 cases of stage Ⅱ,29 cases of stageⅢ. RT- PCR was used to determine the expression of mRNA,Western blotting to determine the expression of proteins. Results PHD3 mRNA was higher in tumor tissues than in adjacent normal lung tissues 〔（ 17. 8 ± 2. 9）vs.（ 7. 1 ± 1. 3） 〕,the difference was statistically significant（ t = 31. 763,P 〈0. 05）; PHD3 protein declined in tumor tissues 〔（ 13. 0 ± 2. 8） vs.（ 20. 7 ± 4. 2） 〕,the difference was statistically significant（ t = 14. 391,P 〈0. 05）. The relative expression of mRNA and protein in lung cancer tissue and NSCLC of different clinical stages of PHD3 weight,the difference was statistically significant（ P 〈0. 05）; with the increase of TNM stage,PHD3 mRNA relative expression quantity was higher,while PHD3 protein expression quantity was relatively low（ P 〈0. 05）. Adjacent normal lung tissue and lymph node metastasis group mRNA and protein in the relative expression of PHD3 comparison,the difference was statistically significant（ P 〈0. 05）;and the lymph node metastasis group PHD3 mRNA relative expression quantity was higher than the adjacent normal lung tissue and without lymph node metastasis group,PHD3 protein expression levels lower（ P 〈0. 05）. The expression of HIF- 1α mRNA was significantly higher in tumor tissues than in adjacent tissues 〔（ 17. 2 ± 2. 9） vs.（ 6. 5 ± 1. 2）,t = 32. 163,P 〈0. 05〕,and HIF- 1α protein higher in tumor tissues than in adjacent tissues 〔（ 20. 9 ± 3. 8） vs.（ 9. 2 ± 1. 8）,t = 26. 251,P 〈0. 05〕. The relative expression of mRNA and protein in lung cancer tissue and NSCLC of different clinical stages of HIF- 1αquantity comparison,the difference was statistically significant（ P 〈0. 05）; with the increase of TNM stage,HIF- 1α mRNA,HIF- 1α protein relative expression quantity was higher（ P 〈0. 05）. Adjacent normal lung tissue and lymph node metastasis group mRNA and protein HIF- 1α relative expression of the comparison,the difference was statistically significant（ P 〈0. 05）;and the lymph node metastasis group mRNA and protein HIF- 1α relative expression quantity was higher than the adjacent normal lung tissue and the group without lymph node metastasis（ P 〈0. 05）. Linear correlation analysis showed that PHD3 protein negatively（ r =- 0. 746,P 〈0. 05）,that PHD3 mRNA was positively correlated with HIF- 1α protein（ r = 0. 792,P 〈0. 05）.Conclusion PHD3 may down- regulate HIF- 1α expression during the development of NSCLC,which can be a target for NSCLC therapy.
出处
《中国全科医学》
CAS
CSCD
北大核心
2014年第33期3948-3952,共5页
Chinese General Practice
关键词
脯氨酰羟化酶
低氧诱导因子1Α
癌
非小细胞肺
逆转录聚合酶链反应
免疫印迹法
Prolyl hydroxylases
Hypoxia-inducible factor 1α
Carcinoma
non-small-cell lung
Reverse tran-scriptase polymerase chain reaction
Immunoblotting
