非小细胞肺癌中缺氧诱导因子-1α和p-糖蛋白的表达及其与人乳头状瘤病毒感染的相关性

Expression of HIF-1α and p-gp in non-small cell lung cancer and their relationship with HPV infection

目的缺氧诱导因子-1α(hypoxia inducible factor-1α,HIF-1α)、p-糖蛋白(p-glycoprotein,p-gp)的表达,HPV感染在非小细胞肺癌(non-small cell lung cancer,NSCLC)发生发展中的作用及三者的相互关系尚不清楚。文中研究NSCLC中HIF-1α和p-gp的相关性,探讨HIF-1α和p-gp在NSCLC发生发展及多药耐药(multidrug resistance,MDR)中的作用,并初步分析HIF-1α和p-gp与人乳头状瘤病毒(human papillomavirus,HPV)感染的相关性。方法收集秦皇岛市第一医院2012年1-5月NSCLC新鲜标本60例作为NSCLC组,20例肺良性病变组织作为肺良性病变组,应用PCR方法选用HPV16、18型特异性引物检测2组中HPV DNA的表达,应用免疫组化法检测HIF-1α、p-gp的表达。结果 NSCLC中HIF-1α阳性率为48.3%(29/60),肺良性病变未见阳性表达(χ2=15.163,P<0.05);p-gp的阳性率为60.0%(36/60),肺良性病变未见阳性表达(χ2=21.818,P<0.05);HIF-1α阳性者中p-gp的表达率明显高于HIF-1α阴性者,两者呈正相关(r=0.313,P<0.05);NSCLC组中HIF-1α表达与组织分化程度及淋巴结转移相关;p-gp表达与组织学分型相关,肺腺癌p-gp阳性表达率(83.3%)高于肺鳞癌(50.0%),差异有统计学意义(P<0.05)。NSCLC高分化型HPV DNA检出率(8.3%)低于中、低分化型(50.0%),差异有统计学意义(P<0.05)。淋巴结转移者HPV DNA检出率(60.6%)高于无淋巴结转移者(23.3%),差异有统计学意义(P<0.05)。结论 HIF-1α与p-gp参与了NSCLC的发生发展及MDR;HPV感染可能是NSCLC发生的病因学因素之一,但NSCLC中HIF-1α、p-gp表达与HPV感染均无协同作用。

Objective The effect of hypoxia inducible factor-1α（ HIF-1α） , p-glycoprotein （ p-gp） and human papillomavir-us（HPV） infection on non-small cell lung cancer （NSCLC） and their interrelationship are still not clear .The article aimed to study the relationship between HIF-1αand P-gp, their role in the occurrence , development and multidrug resistance of NSCLC , as well as the in-terrelationship among HIF-1α, p-gp expression and HPV infection . Methods By using immunohistochemistry , the expression of HIF-1αand p-gp was detected in 60 NSCLC tissues and 20 benign lung disease tissues .PCR was employed to detect the expression of HPV16/18 DNA. Results The positive expression rate of HIF-1αand p-gp was 48.3% and 60.0% respectively in NSCLC, but there was no positive expression of HIF-1αand p-gp detected in the benign lung disease group （P〈0.05）.The positive expression rate of p-gp in HPV DNA positive group and negative group was 64.0% and 57.1%respectively, which showed no significant difference too （P〉0.05）. Conclusion HIF-1αand p-gp are involved in the occurrence, development and multidrug resistance of NSCLC .HPV infection may be one of the etiological factors in the carcinogenesis of NSCLC . However , neither the HIF-1αexpression nor the p-gp expression is associated with HPV infection .