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背景与目的多药耐药是肺癌化疗治疗失败的重要原因,ABC介导药物外排是耐药的主要因素,寻找该家族中新的耐药蛋白并阐明其耐药机制十分重要。ABCG4有望成为耐药候选基因;耐药性与细胞内外pH值可能有关,而V-ATPase在调节pH值起主要作用。本研究通过检测ABCG4和V-ATPase在非小细胞肺癌中的表达,分析其与病理分级和TNM分期间的关系以及两蛋白表达的相关性,为研究ABCG4、V-ATPase在肿瘤表达及耐药相关性提供基础。方法采用免疫组化EnVinsion法、免疫荧光法检测在肺鳞癌、腺癌中的表达,激光共聚焦显微镜观察其定位和共定位,用统计学分析表达差异性和相关性。结果ABCG4在肺鳞癌、腺癌中高表达,两者差异性显著(P=0.001);鳞癌Ⅱ和Ⅱ-Ⅲ组间、腺癌不同分化组间差异性显著;鳞癌和腺癌TNM分期秩和检验差异性显著。V-ATPase在鳞癌、腺癌中也为高表达,两者差异性非常显著;鳞癌Ⅱ和Ⅱ-Ⅲ组间、腺癌不同分化组间差异性显著;在鳞癌和腺癌TNM分期秩和检验差异性均不显著。ABCG4和V-ATPase蛋白在鳞癌、腺癌、鳞癌Ⅱ和Ⅱ-Ⅲ、中分化腺癌各组中的表达相关性检验P<0.01,相关系数rs分别为0.771、0.765、0.714、0.777、0.865;而低分化腺癌组中的相关性检验P值为0.048,相关系数rs为0.350。ABCG4主要定位在胞膜上和胞质中,两蛋白有共定位现象。结论ABCG4和V-ATPase在非小细胞肺癌中高表达,表达的高低与病理分级、TNM分期有关;两蛋白在鳞癌、腺癌及其分级间表达都存在相关性,可能存在相互作用的现象。这为研究ABCG4和V-ATPase在肿瘤中的表达及可能耐药作用提供了实验依据。
BACKGROUND & OBJECTIVE: Multidrug resistance (MDR) is an important cause of failure of chemotherapy in lung cancer. ABC-mediated drug efflux is the main factor of drug resistance. It is very important to find out the new drug resistance in this family and elucidate the mechanism of drug resistance. ABCG4 is expected to become a resistance candidate gene; drug resistance and pH inside and outside the cell may be related to the V-ATPase in the regulation of pH played a major role. This study was designed to investigate the relationship between ABCG4 and V-ATPase expression in non-small cell lung cancer (NSCLC), the relationship between ABCG4 and V-ATPase and the pathological grade and TNM stage, Relevance provides the basis. Methods Immunohistochemical EnVionion method was used to detect the expression in lung squamous cell carcinoma and adenocarcinoma by immunofluorescence. The localization and colocalization were observed by laser scanning confocal microscopy. The difference and correlation were analyzed by statistics. Results The expression of ABCG4 in squamous cell carcinoma and adenocarcinoma was significantly higher than that in adenocarcinoma (P = 0.001). There were significant differences among different differentiation groups of squamous cell carcinoma Ⅱ and Ⅱ-Ⅲ, Rank sum test significant difference. V-ATPase is also highly expressed in squamous cell carcinoma and adenocarcinoma, the difference between the two is very significant; between squamous cell carcinoma Ⅱ and Ⅱ-Ⅲ group, there is significant difference among different differentiation groups; Rank sum test differences were not significant. The correlation between the expression of ABCG4 and V-ATPase in squamous cell carcinoma, adenocarcinoma, squamous cell carcinoma Ⅱ and Ⅱ-Ⅲ, moderately differentiated adenocarcinoma was statistically significant (P <0.01), the correlation coefficient rs was 0.771,0.765,0.714,0.777, 0.865, while in poorly differentiated adenocarcinoma, the P value was 0.048 and the correlation coefficient rs was 0.350. ABCG4 mainly located in the membrane and cytoplasm, the two proteins co-localization phenomenon. Conclusions ABCG4 and V-ATPase are highly expressed in non-small cell lung cancer (NSCLC). The expression of ABCG4 and V-ATPase is related to the pathological grade and TNM stage. There is a correlation between the expression of ABCG4 and V-ATPase in squamous cell carcinoma, adenocarcinoma and their grading. This provides an experimental basis for studying the expression of ABCG4 and V-ATPase in tumor and possible drug resistance.