Zhang Li, Yang Hong, Dong Dandan
Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R.China.
Zhongguo Fei Ai Za Zhi. 2006 Feb 20;9(1):60-4. doi: 10.3779/j.issn.1009-3419.2006.01.15.
Multidrug resistance (MDR) is not only the main reason of the failure of chemotherapy, but also the largest obstacle of the increase of survival rate in lung cancer. MDR of lung cancer is a complex procedure involved in multiple genes and mutiple pathways. Combined examination of resistance-related genes in lung cancer tissues has an important clinical significance. The aim of this study is to explore the relationship among the expression, coexpression of five multidrug resistance factors of lung cancer tissues and clinicopathological characteristics in patients with lung cancer.
Immunohistochemical staining (EnVision method) was used to evaluated the expression of lung resistance protein (LRP), P-glycoprotein (P-gp), glutathione S-transferaseπ (GST-π), topoisomeraseII(TopoII), and multidrug-resistance-associated protein (MRP) in cancer tissues from 72 patients with lung cancer.
The positive rate of LRP, P-gp, GST-π, TopoII and MRP was 79.2%, 86.1%, 54.2%, 29.2% and 30.6% respectively. There was a significant difference of the expression of LRP and TopoII in different sex (Chi-square=11.460 and 4.877, P=0.001 and 0.027), of the expression of LRP, GST-π and TopoII in NSCLC and SCLC (Chi-square=15.104, 14.076 and 9.409, P=0.001, 0.001 and 0.009), of the expression of GST-π in various grade of cell differentiation (Chi-square=8.933,P=0.011), of the expression of TopoII in various T staging (Chi-square=3.963,P=0.049). Spearman analysis of rank relativity showed that there was a better relativity between the expression of LRP, TopoIIand sex (r=0.464 and -0.205, P=0.000 and 0.027), between the expression of LRP, GST-π, TopoII and histology. The expression of LRP and GST-π was significantly higher in NSCLC than in SCLC (r=-0.390 and -0.262, P=0.000 and 0.018), the expression of LRP was significantly higher in adenocarcinoma than in squamous cell carcinoma (r =0.604, P=0.000). The expression of GST-π and TopoII was significantly higher in squamous cell carcinoma than in adenocarcinoma (r =-0.257 and -0.264, P=0.015 and 0.012). There was a reverse relativity between the expression of GST-π and cell differentiation (r =-0.232, P= 0.012 ). There was a positive relativity between the expression of TopoII and T staging (r =0.200, P= 0.031 ) and a reverse relativity between the expression of GST-π and T staging (r =-0.182, P=0.050). Spearman analysis of rank relativity of five multidrug resistance factors' coexpression showed that there was a positive relativity beween LRP and P-gp, LRP and MRP, P-gp and GST-π, P-gp and MRP, GST-π and MRP (r = 0.283 , 0.234, 0.453, 0.204 and 0.323, P=0.002, 0.011, 0.000, 0.027 and 0.000), the coexpression rate was 70.8%, 27.8%, 52.8%, 29.2%, 23.6% respectively. There was a reverse relativity between LRP and TopoII (r =-0.183, P=0.048), and the coexpression rate was 19.4%.
The expression of partial multidrug resistance factors is relative significantly to sex, histology and cell differentiation, but not to T, N, M stage and clinical stage. The higher coexpression rate and positive relativity indicate MDR in lung cancer is affected by various multidrug resistance factors. It is important to detect coalescently various multidrug resistance factors.
多药耐药（MDR）不仅是化疗失败的主要原因，也是肺癌生存率提高的最大障碍。肺癌的多药耐药是一个涉及多个基因和多条途径的复杂过程。联合检测肺癌组织中与耐药相关的基因具有重要的临床意义。本研究旨在探讨肺癌组织中五种多药耐药因子的表达、共表达与肺癌患者临床病理特征之间的关系。
采用免疫组织化学染色（EnVision法）检测72例肺癌患者癌组织中肺耐药蛋白（LRP）、P-糖蛋白（P-gp）、谷胱甘肽S-转移酶π（GST-π）、拓扑异构酶II（TopoII）和多药耐药相关蛋白（MRP）的表达。
LRP、P-gp、GST-π、TopoII和MRP的阳性率分别为79.2%、86.1%、54.2%、29.2%和30.6%。LRP和TopoII在不同性别中的表达有显著差异（卡方=11.460和4.877，P=0.001和0.027），LRP、GST-π和TopoII在非小细胞肺癌（NSCLC）和小细胞肺癌（SCLC）中的表达有显著差异（卡方=15.104、14.076和9.409，P=0.001、0.001和0.009），GST-π在不同细胞分化程度中的表达有显著差异（卡方=8.933，P=0.011），TopoII在不同T分期中的表达有显著差异（卡方=3.963，P=0.049）。Spearman等级相关性分析显示，LRP、TopoII与性别之间有较好的相关性（r=0.464和-0.205，P=0.000和0.027），LRP、GST-π、TopoII与组织学之间有相关性。LRP和GST-π在NSCLC中的表达显著高于SCLC（r=-0.390和-0.262，P=0.000和0.018），LRP在腺癌中的表达显著高于鳞状细胞癌（r=0.604，P=0.000）。GST-π和TopoII在鳞状细胞癌中的表达显著高于腺癌（r=-0.257和-0.264，P=0.015和0.012）。GST-π与细胞分化之间呈负相关（r=-0.232，P=0.012）。TopoII与T分期之间呈正相关（r=0.200，P=0.031），GST-π与T分期之间呈负相关（r=-0.182，P=0.050）。Spearman等级相关性分析显示，五种多药耐药因子共表达之间，LRP与P-gp、LRP与MRP、P-gp与GST-π、P-gp与MRP、GST-π与MRP之间呈正相关（r=0.283、0.234、0.453、0.204和0.323，P=0.002、0.011、0.000、0.027和0.000），共表达率分别为70.8%、27.8%、52.8%、29.2%、23.6%。LRP与TopoII之间呈负相关（r=-0.183，P=0.048），共表达率为19.4%。
部分多药耐药因子的表达与性别、组织学和细胞分化显著相关，但与T、N、M分期及临床分期无关。较高的共表达率和正相关性表明肺癌的多药耐药受多种多药耐药因子影响。联合检测多种多药耐药因子具有重要意义。
