Association of expression of MRP1, BCRP, LRP and ERCC1 with outcome of patients with locally advanced non-small cell lung cancer who received neoadjuvant chemotherapy.
OBJECTIVE
The aim of this study was to investigate prognostic value of multidrug resistance protein 1 (MRP1), breast cancer resistance protein (BCRP), lung resistance-related protein (LRP) and excision repair cross-complementing 1 (ERCC1) in patients with locally advanced non-small cell lung cancer (NSCLC) who received neoadjuvant cisplatin-based chemotherapy.


METHODS
Transbronchial biopsy (TBB) specimens from 46 patients with stage IIIA (N(2)) NSCLC were collected to determine the expression level of MRP1, BCRP, LRP and ERCC1 mRNA by semiquantitative RT-PCR. The expression level of each gene was analyzed in relation to histopathologic response to chemotherapy, and tumor-free survival (TFS) and overall survival.


RESULTS
Patients with MRP1 or LRP low expression had a significantly better histopathologic response (P=0.032 and 0.006), and a significantly longer TFS (P=0.043 and 0.025) and overall survival (P=0.019 and 0.013) than those with MRP1 or LRP high expression. Patients with ERCC1 low expression had a significantly longer overall survival (P=0.007), but not TFS (P=0.094) than those with ERCC1 high expression. In multivariate analysis, LRP low expression was a significantly favorable factor for TFS (P=0.027), and LRP and ERCC1 were significantly favorable factors for overall survival (P=0.012 and 0.032).


CONCLUSIONS
Assessment of MRP1 and LRP mRNA expression in TBB specimens may predict histopathologic response and survival in locally advanced NSCLC patients who received neoadjuvant cisplatin-based chemotherapy. ERCC1 expression was predictive for overall survival.
Li
Jian
J
Department of Pulmonary Medicine, Affiliated Hospital of Jiangsu University, 438 North Jiefang Road, Zhenjiang 212001, China. lijian541226@163.com
Li
Zhen-Nan
ZN
Yu
Li-Chao
LC
Bao
Qian-Lei
QL
Wu
Jian-Rong
JR
Shi
Shun-Bing
SB
Li
Xiao-Qin
XQ
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D018572:Disease-Free Survival; D004720:Endonucleases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009367:Neoplasm Staging; D011379:Prognosis; D016896:Treatment Outcome; D020394:Vault Ribonucleoprotein Particles / Q000235:genetics / Q000378:metabolism*; 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