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The background and purpose of lung tumor is a common cause of death in non-small cell lung cancer (non-small cell lung cancer, NSCLC) accounts for 75% of all lung cancer. More than half of the patients found late (Ⅲ B or Ⅳ), lost the chance of operation, therefore chemotherapy become lung cancer treatment, However tumor cells tolerated the drug has led to the failure of lung cancer chemotherapy. In vitro studies show that the main mechanism by increased drug transporters mediated drug efflux of NSCLC resistant drug transporter protein found mainly ABC transporter protein family of P-glycoprotein (P-glycoprotein, P-gp), multi- multidrug resistance-associated protein (multidrug resistance protein1, MRP1) and breast cancer resistance protein (breast cancer resistance protein, BCRP). P-gp, MRP1 and BCRP as drug transporters in drug-resistant tumor cells were found, and proved to be the important mechanism mediated by the multidrug resistance (multidrug resistance, MDR) in clinical cancer chemotherapy process. In vitro studies have found different, the three drugs transporter protein expression mediated tumor cell drug resistance spectrum, such as: P-gp-mediated alkaloids, antitumor antibiotic the podophyllum neomycin class, paclitaxel, and alkylating agents such as drug resistance; of MRP1 drug transporter spectrum similar to P-gp, but the the paclitaxel transit is not as good as the P-gp; of BCRP overexpression can lead to drug-sensitive cells, topotecan the health, irinotecan, SN- 38 (irinotecan's active metabolite), mitoxantrone, doxorubicin resistance, while still sensitive to vincristine, paclitaxel and cisplatin. To learn more about the P-gp, MRP1 and BCRP in NSCLC role in the development process, and its expression and clinical tumor tissue of 66 cases of pathological and clinical data NSCLC patients before treatment resistance protein expression detection, to explore the relationship of the drug transporter protein expression was correlated with clinical and pathological features, and to assess their potential clinical application in the judgment chemosensitivity, and its expression on the prognosis of patients with NSCLC. Materials and methods to collect complete clinical data from 2003 to 2005, Henan Tumor Hospital 66 cases of primary non-small cell lung cancer cases, be detected tumor specimens were paraffin-embedded tissue, of which, 34 cases of surgical specimens, bronchoscopy specimens 32 cases. All patients were newly diagnosed and were not accept patients undergoing preoperative radiotherapy and chemotherapy. By immunohistochemical SP method to detect P-gp, MRP1, BCRP expression in the lung tissue. Normal lung tissue known as a positive control. By two immunohistochemical room pathologists in do not know of any clinical and pathological data using semi-quantitative method for immunohistochemical staining to assess. Pathological type of assessment is based on the WHO standard assessment based on chest X-ray of the chest or abdominal CT, brain CT or MRI, whole body bone scan, clinical stage of the current general international staging before treatment. Into the group of patients diagnosed with a median age of 56 years (range 35-75 years). All advanced NSCLC patients receiving standard platinum-based combination chemotherapy regimen. All enrolled patients with a median follow-up time of 311 days (range 31-759 days). P-gp, MRP1 and BCRP expression and clinical pathological features were used univariate logistic regression analysis using SAS 8.1 statistical analysis software; resistance protein expression and the relationship of the effect of chemotherapy was assessed using logistic regression analysis; univariate survival analysis obtained using the Kaplan-Meier method, and survival curves; multivariate survival analysis using multivariate Cox regression model for the stepwise; All statistical analysis are used α = 0.05 is significant with test standards. Overall survival time was defined as the time from diagnosis to death. Results 1. P-gp, MRP1, BCRP expression in NSCLC and its relationship with clinicopathological features. 66 patients with NSCLC tissue P-gp, MRP1 and BCRP total positive expression rate of 40.91%, 72.73% and 43.94%, respectively. NSCLC tissue P-gp expression rate of women than men, as age increased expression rate, non-smoking patients with high expression in patients with a history of smoking, adenocarcinoma than squamous cell carcinoma; MRP1 expression in adenocarcinoma higher than squamous cell carcinoma; of BCRP expression with clinicopathological characteristics unrelated. 2. P-gp, MRP1, BCRP expression of the effect of chemotherapy in patients with NSCLC. 32 cases of clinical evaluation of lesions of NSCLC patients evaluable for response after 2 cycles of chemotherapy resistance protein expression and the effect of chemotherapy in patients with relations. Discovery of BCRP expression and the effect of chemotherapy in patients related (OR = 5.042,95% CI = 1.107 to 22.9660); MRP1 and P-gp expression in patients regardless of the effect of chemotherapy (OR = 5.000,1.016; 95% CI = 0.826 ~~ 30.277,0.253 to 4.084). 3. P-gp, MRP1, BCRP expression affect prognosis and survival of patients with NSCLC. Found in the survival analysis including all cases, TNM stage later shorter the survival time (β = 1.14397, P = 0.0002, HR = 3.139), P-gp and MRP1 expression in patients with positive than negative patients survive for a long time ( β = -1.05599, P = 0.0445, HR = 0.348), and patients with other clinical and pathological features such as: gender, age, smoking history, the pathological type of survival time has no effect; survival in the grouping of different pathological types of cases analysis found in adenocarcinoma group, TNM staging more late survival time is shorter (β = 2.66275, P = 0.0324, HR = 14.336), the expression of P-gp-positive patients than in patients with negative survival time length (β = -2.62840 , P = 0.0426, HR = 0.072); squamous cell carcinoma group failed to find clinical and pathological features and survival time. Conclusion 1. BCRP can be used as predictors to determine the effect of chemotherapy in patients with advanced NSCLC, BCRP can be used as a molecular target for reducing patients with advanced NSCLC chemotherapy drug resistance. 2. P-gp and MRP1 can be used as indicators to predict the prognosis of patients with NSCLC BCRP expression and NSCLC patient prognosis.
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