Kim Young Hak, Ishii Genichiro, Goto Koichi, Ota Shuji, Kubota Kaoru, Murata Yukinori, Mishima Michiaki, Saijo Nagahiro, Nishiwaki Yutaka, Ochiai Atsushi
Pathology Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
Lung Cancer. 2009 Jul;65(1):105-11. doi: 10.1016/j.lungcan.2008.10.008. Epub 2008 Nov 25.
ATP-binding cassette (ABC) transporter and DNA excision repair proteins play a pivotal role in the mechanisms of drug resistance. The aim of this study was to investigate the expression of ABC transporter and DNA excision repair proteins, and to elucidate the clinical significance of their expression in biopsy specimens from patients with small-cell lung cancer (SCLC).
We investigated expression of the ABC transporter proteins, P-glycoprotein (Pgp), multidrug resistance associated-protein 1 (MRP1), MRP2, MRP3, and breast cancer resistance protein (BCRP), and the DNA excision repair proteins, excision repair cross-complementation group 1 (ERCC1) protein and breast cancer susceptibility gene 1 (BRCA1) protein, in tumor biopsy specimens obtained before chemotherapy from 130 SCLC patients who later received platinum-based combination chemotherapy, and investigated the relationship between their expression and both response and survival.
No significant associations were found between expression of Pgp, MRP1, MRP2, MRP3, ERCC1, or BRCA1 and either response or survival. However, there was a significant association between BCRP expression and both response (p=0.026) and progression-free survival (PFS; p=0.0103).
BCRP expression was significantly predictive of both response and progression-free survival (PFS) in SCLC patients receiving chemotherapy. These findings suggest that BCRP may play a crucial role in drug resistance mechanisms, and that it may serve as an ideal molecular target for the treatment of SCLC.
ATP结合盒（ABC）转运蛋白和DNA切除修复蛋白在耐药机制中起关键作用。本研究旨在调查ABC转运蛋白和DNA切除修复蛋白的表达情况，并阐明它们在小细胞肺癌（SCLC）患者活检标本中表达的临床意义。
我们调查了130例后来接受铂类联合化疗的SCLC患者化疗前获得的肿瘤活检标本中ABC转运蛋白P-糖蛋白（Pgp）、多药耐药相关蛋白1（MRP1）、MRP2、MRP3和乳腺癌耐药蛋白（BCRP）以及DNA切除修复蛋白切除修复交叉互补组1（ERCC1）蛋白和乳腺癌易感基因1（BRCA1）蛋白的表达情况，并研究了它们的表达与反应和生存之间的关系。
未发现Pgp、MRP1、MRP2、MRP3、ERCC1或BRCA1的表达与反应或生存之间存在显著关联。然而，BCRP表达与反应（p=0.026）和无进展生存期（PFS；p=0.0103）均存在显著关联。
BCRP表达对接受化疗的SCLC患者的反应和无进展生存期（PFS）具有显著预测作用。这些发现表明，BCRP可能在耐药机制中起关键作用，并且可能成为治疗SCLC的理想分子靶点。
