Association between multidrug resistance-associated protein 1 and poor prognosis in patients with nasopharyngeal carcinoma treated with radiotherapy and concurrent chemotherapy.
ATP-binding cassette (ABC) multidrug transporters have been associated with chemoresistance, which is a major obstacle in attempts to improve clinical outcome of patients with nasopharyngeal carcinoma (NPC). In this study, we investigated 3 ABC multidrug transporters including MDR1, MRP1, and BCRP for their potential as prognostic indicators in patients with NPC. We examined the protein expression profiles of MDR1, MRP1, and BCRP in NPC tissues from 60 patients with advanced stages who were treated with radiotherapy and concurrent chemotherapy. The clinicopathologic features, patterns of treatment failure, and survival data were compared with the transporter expression. Univariate analyses were performed to determine the prognostic factors that influenced treatment failure and patient survival. We found that MRP1 expression was strongly predictive of both 5-year survival (P = .025) and disease-free survival (P < .001). However, neither MDR1 nor BCRP expression was correlated with the clinicopathologic parameters. Interestingly, the incidence of recurrence and metastasis for patients in the MRP1-positive group was significantly higher than that in the MRP1-negative group (P = .003). With multivariate analysis, MRP1 expression at the time of diagnosis before the treatment was identified as an independent prognostic factor for both 5-year survival (P = .041) and disease-free survival (P = .001). MRP1 expression can therefore be used as a potent molecular risk factor and a guide for chemotherapeutic regimens in patients with advanced stages of NPC.
Larbcharoensub
Noppadol
N
Department of Pathology, Faculty of Medicine at Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Leopairat
Juvady
J
Sirachainan
Ekaphop
E
Narkwong
Ladawan
L
Bhongmakapat
Thongchai
T
Rasmeepaisarn
Kawin
K
Janvilisri
Tavan
T
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000230:Adenocarcinoma / Q000378:metabolism / Q000401:mortality / Q000628:therapy; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000628:therapy*; D009363:Neoplasm Proteins / Q000378:metabolism; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000378:metabolism; D018714:Radiotherapy, Adjuvant; D015996:Survival Rate
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D014408:Biomarkers, Tumor; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C116614:ABCG2 protein, human; C421109:multidrug resistance-associated protein 1