Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study
Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study
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DOI：
10.1016/s1470-2045(06)70732-x
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发表时间：
2006-07-01
期刊：
影响因子：
51.1
通讯作者：
Wu, Chin-Lee
中科院分区：
文献类型：
--
作者：
Jiang, Zhong;Chu, Peigou G.;Wu, Chin-Lee
背景 远处转移是肾细胞癌死亡的主要原因，而肿瘤的转移潜力往往是不可预测的。我们的目的是研究IMP3（一种癌胎儿RNA结合蛋白）是否可以作为预测肾细胞癌转移和预后的生物标志物。方法我们研究了501个原发性和转移性肾细胞肿瘤。通过生存分析对 371 名局部原发性肿瘤患者进行了进一步调查。我们通过免疫组织化学评估了肿瘤组织中 IMP3 的表达，并通过定量实时 PCR 和蛋白质印迹分析评估了选定组织中 IMP3 mRNA 和蛋白的表达。结果与非转移性肾细胞肿瘤相比，IMP3 表达不仅在转移性肿瘤中大大增加，而且在原发性肿瘤的子集中也显着增加。随后可能发生转移。不表达 IMP3 的原发性局部肿瘤患者比表达 IMP3 的肿瘤患者具有更长的无转移生存期和总生存期 (p < 0(.)0001)。 IMP3 阳性局部肿瘤患者的 5 年无转移生存率比 IMP3 阴性肿瘤患者低得多（I 期肿瘤，44% vs 98%，风险比 17(.)18 [95% CI 7.82-37(.)78]；II 期，41% vs 94%，10(.)14 [3(.)46-29(.)68]；第三阶段， 16% 与 62%，4(.)04 [2(.)23-7(.)31])。 IMP3 表达还与 5 年总生存率降低相关（I 期，32% vs 89%，6(.)44 [3(.)63-11(.)42]；II 期，41% vs 88%，6(.)93 [2(.)63-18(.)27]；III 期，14% vs 58%，3(.)46 [1(.)98-6(.)05])。原发肿瘤中 IMP3 状态（阳性与阴性）的多变量分析显示，无转移生存的风险比为 5(.)84 (95% CI 3(.)60-9(.)49)，总生存的风险比为 4(.)01 (2(.)66-6(.)05)（均 p < 0(.)0001），远高于与其他独立危险因素相关的风险比。 IMP3 是一种独立的预后标志物，可用于肾细胞癌的初步诊断，以确定极有可能发生转移以及可能从早期全身治疗中受益的患者。
Background Distant metastasis is the main cause of death from renal-cell carcinoma, and the metastatic potential of tumours is often unpredictable. We aimed to investigate whether IMP3, an oncofetal RNA-binding protein, can be used as a biomarker to predict metastasis and prognosis of renal-cell carcinoma.Methods We studied 501 primary and metastatic renal-cell tumours. 371 patients with localised primary tumours were further investigated by use of survival analysis. We assessed IMP3 expression in tumour tissues by immunohistochemistry, and IMP3 mRNA and protein expression in selected tissues by quantitative real-time PCR and western blot analysis.Findings Compared with non-metastatic renal-cell tumours, IMP3 expression was greatly increased not only in metastatic tumours but also in a subset of primary tumours; that were likely to subsequently develop metastases. Patients with primary localised tumours that did not express IMP3 had a longer metastasis-free survival and overall survival than did those with tumours expressing IMP3 (p < 0(.)0001). Patients with IMP3-positive localised tumours had a much lower 5-year metastasis-free survival than did those with IMP3-negative tumours (for stage I tumours, 44% vs 98%, hazard ratio 17(.)18 [95% CI 7.82-37(.)78]; stage II, 41% vs 94%, 10(.)14 [3(.)46-29(.)68]; stage III, 16% vs 62%, 4(.)04 [2(.)23-7(.)31]). IMP3 expression was also associated with reduced 5-year overall survival (stage I, 32% vs 89%, 6(.)44 [3(.)63-11(.)42]; stage II, 41% vs 88%, 6(.)93 [2(.)63-18(.)27]; stage III, 14% vs 58%, 3(.)46 [1(.)98-6(.)05]). Multivariable analysis of IMP3 status (positive vs negative) in primary tumours showed hazard ratios of 5(.)84 (95% CI 3(.)60-9(.)49) for metastasis-free survival and 4(.)01 (2(.)66-6(.)05) for overall survival (both p < 0(.)0001), which were much higher than hazard ratios associated with other independent risk factors.Interpretation IMP3 is an independent prognostic marker that can be used at initial diagnosis of renal-cell carcinoma to identify patients who have a high potential to develop metastasis and who might benefit from early systemic treatment.