P16及FHIT基因异常表达在非小细胞肺癌发病机制中的研究  

Abnormal expression of P16 and FHIT genes in pathogenesis of non-small cell lung cancer

作　　者：佘天宇 佘真真 徐海涛[1] 刘帅[1] 贾腾 张庆广[1] 李文晶 SHE Tian-yu;SHE Zhen-zhen;XU Hai-tao;LIU Shuai;JIA Teng;ZHANG Qing-guang;LI Wen-jing(Department of Oncology,The Affiliated Hospital,Binzhou Medical College,Binzhou 256600,China;Department of Thoracic Surgery,The Affiliated Hospital,Binzhou Medical College,Binzhou 256600,China;Department of General Surgery,Wudi People's Hospital,Wudi 251900,China)

机构地区：[1]滨州医学院附属医院胸外科,山东滨州256600 [2]滨州医学院附属医院肿瘤科,山东滨州256600 [3]山东省无棣县人民医院普外科,山东滨州251900

出　　处：《实用医院临床杂志》2020年第5期1-5,共5页Practical Journal of Clinical Medicine

摘　　要：目的探讨P16及FHIT基因异常表达在非小细胞肺癌(NSCLC)的发病机制。方法选取肺癌切除术NSCLC患者65例,收集NSCLC肿瘤组织标本、正常肺组织标本。采用聚合酶链式反应(PCR)扩增DNA,采用变性聚丙烯酰胺凝胶电泳-硝酸银染色法检测基因杂合性缺失,采用限制性内切酶法检测DNA甲基化,采用免疫组化法检测蛋白表达。结果NSCLC组织P16及FHIT基因杂合性缺失发生率为58.46%和70.77%,甲基化发生率为49.23%和66.15%,蛋白表达缺失率为67.69%和72.31%;正常肺组织未见P16及FHIT基因杂合性缺失、甲基化、蛋白表达缺失,差异有统计学意义(P<0.05)。P16基因杂合性缺失及甲基化与P16蛋白表达缺失具有关联;FHIT基因杂合性缺失及甲基化与FHIT蛋白表达缺失具有关联(P<0.05)。临床分期是P16蛋白表达缺失的独立影响因素;性别、吸烟史是FHIT蛋白表达缺失的独立影响因素(P<0.05)。结论P16及FHIT基因异常表达在NSCLC的发生发展中起重要作用,发病机制可能与P16及FHIT基因的杂合性缺失和甲基化导致的P16及FHIT蛋白表达缺失有关。Objective To explore the pathogenesis of non-small cell lung cancer(NSCLC)with the abnormal expression of P16 and FHIT genes.Methods A total of 65 NSCLC patients who underwent lung cancer resection were enrolled.The specimens of NSCLC tumor tissues and normal lung tissues were collected.Polymerase chain reaction(PCR)was applied to amplify DNA.The loss of gene heterozygosity was detected by polyacrylamide gel electrophoresis-silver nitrate staining.DNA methylation was detected by restriction endonuclease.The expression of proteins was detected by immunohistochemistry.Results In NSCLC tissues,incidence rates of heterozygosity loss of P16 and FHIT genes were 58.46%and 70.77%,methylation was 49.23%and 66.15%and protein expression deletion was 67.69%and 72.31%,respectively.In P16 and FHIT genes of normal lung tissues,there were no heterozygosity loss,methylation and protein expression deletion(P<0.05).The heterozygosity loss and methylation of P16 gene were related with expression deletion of P16 protein(P<0.05).The heterozygosity loss and methylation of FHIT gene were related with expression deletion of FHIT protein(P<0.05).The clinical stage was the independent factor of P16 protein expression deletion(P<0.05).The gender and smoking history were the independent factor of FHIT protein expression deletion(P<0.05).Conclusion The abnormal expression of P16 and FHIT genes plays important roles in the occurrence and development of NSCLC.The pathogenesis may be related to the expression deletion of P16 and FHIT protein induced by their heterozygosity loss and methylation.

关 键 词：非小细胞肺癌 P16基因 FHIT基因 杂合性缺失 甲基化 

分 类 号：R734.2[医药卫生—肿瘤]