Clinical Observations
THE CORRELATION BETWEEN THE EXPRESSION OF MULTIDRUG RESISTANCE RELATED GENE AND CELL APOPTOSIS AND CLINICAL SIGNIFICANCE IN NON-SMALL CELL LUNG CANCER
Abstract
Objective: To explore the correlation and clinical significance between expression of MDR (multidrug resistance) related gene MRP, MDRI, C-erbB-2 and cell apoptosis in non-small cell lung cancer (NSCLC).
Methods: RT-PCR, Immunohistochemistry were used to examine the expression of mRNA and protein in the MDR and apoptosis related gene. Apoptosis cells were assayed by Terminal deoxynucleotidyl transferase (TdT)- mediated biotin dUTP nick end-labeling (TUNEL).
Results: The positive rates of MRP, MDRI, C-erbB-2, bcl-2, C-myc mRNA in 63 cases NSCLC were 81.0% (51/63), 38.1%(24/63), 47.6 % (30/63), 65.1%(41/63), 76.2%(48/63) respectively. Their levels were higher than those of corresponding proteins (74.6%, 34.9%, 46.0%, 61.9%, 71.4%, respectively). The significant association was found between the mRNA level and the protein expression (r=+0.764, P<0.02). The C-myc expression in 2 cases adjacent and benign lung tissue were light positive, and another 3 cases were negative. The positive correlation were demonstrated between C-mye and C-erbB-2 (r=+0.547, p=0.001) as well as bci-2 and C-erbB-2 (r=+0.486, p=0.023) in NSCLC. There is no any correlation among bcl-2, C-myc and MRP or MDR1. There exists inverse correlation between apoptotic index and bcl-2 (r=-0.587, p = 0.017), and no any correlation among apoptotic index and MRP or MDR1 or C-erbB-2 or C-myc. The average apoptotic index were higher in the effective chemotherapy group (27.2±2.1, 30.5±1.8) than that in the non-effective chemotherapy group (9.4±1.3, 12.6±2.4) with adenocarcinoma and squamous cell carcinoma (p=0.01, p=0.004). The positive rates of bcl-2, MRP, C-erbB-2 expression in the effective chemotherapy group (31.8%, 40.9%, 22.7%, respectively) were lower than those in the non-effective chemotherapy group (77.4%, 90.3%, 67.7%, respectively) (p=0.036, p=0.012, p=0.01), but MDRI and C-myc expression have no any significant difference (p=0.067, p=0.282). The median survival time in the patients with coexpression of more than three MDR and/or apoptosis related genes are shorter (8.6 months) than that in those patients with coexpression of less than three MDR and/or apoptosis related genes (15.5 months)(p=0.01).
Conclusion: The multidrug resistance in NSCLC is not only related to many drug resistance genes, but also involved in cell apoptosis and apoptosis related gene expression. The coexpression of MDR and apoptosis related gene is related to the survival time.
Methods: RT-PCR, Immunohistochemistry were used to examine the expression of mRNA and protein in the MDR and apoptosis related gene. Apoptosis cells were assayed by Terminal deoxynucleotidyl transferase (TdT)- mediated biotin dUTP nick end-labeling (TUNEL).
Results: The positive rates of MRP, MDRI, C-erbB-2, bcl-2, C-myc mRNA in 63 cases NSCLC were 81.0% (51/63), 38.1%(24/63), 47.6 % (30/63), 65.1%(41/63), 76.2%(48/63) respectively. Their levels were higher than those of corresponding proteins (74.6%, 34.9%, 46.0%, 61.9%, 71.4%, respectively). The significant association was found between the mRNA level and the protein expression (r=+0.764, P<0.02). The C-myc expression in 2 cases adjacent and benign lung tissue were light positive, and another 3 cases were negative. The positive correlation were demonstrated between C-mye and C-erbB-2 (r=+0.547, p=0.001) as well as bci-2 and C-erbB-2 (r=+0.486, p=0.023) in NSCLC. There is no any correlation among bcl-2, C-myc and MRP or MDR1. There exists inverse correlation between apoptotic index and bcl-2 (r=-0.587, p = 0.017), and no any correlation among apoptotic index and MRP or MDR1 or C-erbB-2 or C-myc. The average apoptotic index were higher in the effective chemotherapy group (27.2±2.1, 30.5±1.8) than that in the non-effective chemotherapy group (9.4±1.3, 12.6±2.4) with adenocarcinoma and squamous cell carcinoma (p=0.01, p=0.004). The positive rates of bcl-2, MRP, C-erbB-2 expression in the effective chemotherapy group (31.8%, 40.9%, 22.7%, respectively) were lower than those in the non-effective chemotherapy group (77.4%, 90.3%, 67.7%, respectively) (p=0.036, p=0.012, p=0.01), but MDRI and C-myc expression have no any significant difference (p=0.067, p=0.282). The median survival time in the patients with coexpression of more than three MDR and/or apoptosis related genes are shorter (8.6 months) than that in those patients with coexpression of less than three MDR and/or apoptosis related genes (15.5 months)(p=0.01).
Conclusion: The multidrug resistance in NSCLC is not only related to many drug resistance genes, but also involved in cell apoptosis and apoptosis related gene expression. The coexpression of MDR and apoptosis related gene is related to the survival time.
