Expression of MRP1, BCRP, LRP, and ERCC1 in advanced non-small-cell lung cancer: correlation with response to chemotherapy and survival.
OBJECTIVE
We investigated the prognostic value of the expression of multidrug resistance protein-1 (MRP1), breast cancer resistance protein (BCRP), lung resistance-related protein (LRP), and excision repair cross-complementing group-1 (ERCC1) in patients with advanced non-small-cell lung cancer (NSCLC) treated with cisplatin-based chemotherapy.


METHODS
Semiquantitative reverse-transcriptase polymerase chain reaction (RT-PCR) was used for detecting the expression of MRP1, BCRP, LRP, and ERCC1 mRNA in 66 transbronchial biopsy (TBB) samples from untreated patients with advanced NSCLC. All of the patients received cisplatin-based chemotherapy. Response to chemotherapy, progression-free survival (PFS), and overall survival (OS) were compared in relation to expression of each gene and clinicopathologic factors.


RESULTS
Results showed that tumor stage (P = .028) and the expression of MRP1 (P = .046) and LRP (P = .012) correlated with response to chemotherapy. Poor performance status (PS; P = .016), advanced tumor stage (P = .004), and the high expression of MRP1 (P = .012) and LRP (P = .002) predicted poorer PFS. Performance status (P = .009); tumor stage (P = .003); and the expression of MRP1 (P = .017), LRP (P = .005), and ERCC1 (P = .002) were predictive for OS. In a Cox proportional hazards multivariable analysis, PS (P = .042), tumor stage (P = .007), and the expression of LRP (P = .011) and ERCC1 (P = .026) were identified as independent prognostic factors for OS.


CONCLUSIONS
Our data suggested that determination of MRP1, LRP, and ERCC1 mRNA expression using RT-PCR in TBB samples might be helpful in predicting outcome of patients with advanced NSCLC treated with cisplatin-based chemotherapy and in optimizing therapeutic strategy based on the expression of these genes.
Li
Jian
J
Department of Pulmonary Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, China. lijian541226@163.com
Li
Zhen-Nan
ZN
Du
Yong-Jie
YJ
Li
Xiao-Qin
XQ
Bao
Qian-Lei
QL
Chen
Ping
P
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000235:genetics; D018572:Disease-Free Survival; D004720:Endonucleases / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D016896:Treatment Outcome; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics; D000099187:Major Vault Protein
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D002945:Cisplatin; D004268:DNA-Binding Proteins; D004720:Endonucleases; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D020394:Vault Ribonucleoprotein Particles; D000099187:Major Vault Protein; C116614:ABCG2 protein, human; C071447:ERCC1 protein, human; C421109:multidrug resistance-associated protein 1