Study on the relationship among multidrug resistance factor expression of lung cancer tissues and clinicopathological characteristics in patients with lung cancer

Abstract

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.