ATP-binding cassette sub-family G member 2 (ABCG2) is a semi-transport protein that plays a major role in multidrug resistance. We aimed to evaluate the prognostic significance of ABCG2 expression in patients with clear cell renal cell carcinoma.

目的:探讨三磷酸腺苷结合转运蛋白G超家族成员2 (ATP-Binding cassette transporter group 2,ABCG2)在肾细胞癌(RCC)临床随访中的意义.方法:从本院肾癌数据库中选择具有完整资料的RCC组织标本110例,患者年龄(56士10)岁(17～80岁),随访时间为(72士30)个月(6～102个月).以10例肾积水失功能的无癌肾组织为对照.使用ABCG2标准试剂盒对所有组织标本进行免疫组织化学染色,并结合临床、病理参数进行回归分析.结果:在110例RCC组织中,62例(56.4％)ABCG2呈阳性表达;在10例非肾癌组织中,ABCG2均呈阴性表达(P＜0.01).RCC组织中ABCG2的表达水平与远处转移和5年存活率密切相关(P＜0.05).RCC患者5年总生存率为79.1％,其中ABCG2阴性者为93.8％,ABCG2阳性者为67.7％ (P＜0.001),两组总生存时间分别为(85.1士22.7)个月和(62.1士32.8)个月(P＜0.oo1).Cox多因素回归分析显示ABCG2是总生存时间的独立预后因子,相对危险度(risk ratio,RR)为2.846 (P＜0.01).结论:ABCG2的表达水平与RCC患者是否有远处转移及5年生存率密切相关,且ABCG2表达越强,RCC患者的预后越差.ABCG2是RCC的独立预后指标,推荐其可作为临床常规随访项目之一.

INTRODUCTON:We wanted to identify the prognostic factors for overall survival (OS) in Chinese patients with metastatic renal cell carcinoma (mRCC) treated with first-line targeted therapy (sorafenib or sunitinib).METHODS:We retrospectively reviewed clinical data from 119 mRCC patients administered sorafenib or sunitinib at the Ruijin Hospital since 2007. OS rates were calculated by the Kaplan-Meier method. Each variable was investigated univariately and then multivariately using a stepwise algorithm. A multivariate Cox regression model analyzed baseline variables for prognostic significance.RESULTS:The mean patient age was 57 ± 12 years; 37 patients (31%) received sorafenib and 82 (69%) received sunitinib. The mean OS was 22.7 ± 15.6 months (range: 2.8- 68.7). OS rates at year 1, 3 and 5 were 74%, 57%, and 36%, respectively. Univariate analysis identified significant negative prognostic factors (p < 0.05) as Eastern Cooperative Oncology Group (ECOG) performance status ≥2, symptoms, no prior nephrectomy, microscopic necrosis, ≥2 metastatic sites, presence of liver, bone, or pancreas metastasis, hemoglobin less than the lower limit of normal(female <115 g/L, male <130 g/L), and serum alkaline phosphatase greater than the upper limit of normal (126 IU/L) at baseline, as well as a relative dose intensity of targeting agents in the first month (1M-RDI) of <50%. Multivariate analysis of OS identified 4 independent predictors: no symptoms, no bone or pancreas metastasis, and 1M-RDI of targeting agents (≥50%).CONCLUSIONS:With targeted therapy, there is some change in the prognostic factors for mRCC and target drug therapies (1M-RDI ≥50%) play an important role in the prognosis of mRCC. Continued progress in the identification of patient-specific prognostic factors for mRCC will require further advances in the understanding of tumour biology.