分析RNA结合蛋白IMP3以预测肾细胞癌的转移和预后：一项回顾性研究。
Analysis of RNA-binding protein IMP3 to predict metastasis and prognosis of renal-cell carcinoma: a retrospective study.
作者信息
Jiang Zhong, Chu Peigou G, Woda Bruce A, Rock Kenneth L, Liu Qin, Hsieh Chung-Cheng, Li Cuizhen, Chen Wengang, Duan Hai Ou, McDougal Scott, Wu Chin-Lee
机构信息
University of Massachusetts Medical Center, Department of Pathology, Worcester, MA, USA.
出版信息
Lancet Oncol. 2006 Jul;7(7):556-64. doi: 10.1016/S1470-2045(06)70732-X.
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.
背景
远处转移是肾细胞癌致死的主要原因，肿瘤的转移潜能往往难以预测。我们旨在研究一种癌胚RNA结合蛋白IMP3是否可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例原发性和转移性肾细胞肿瘤。对371例局限性原发性肿瘤患者进一步进行生存分析。我们通过免疫组织化学评估肿瘤组织中IMP3的表达，并通过定量实时PCR和蛋白质印迹分析评估选定组织中IMP3的mRNA和蛋白质表达。
结果
与非转移性肾细胞肿瘤相比，IMP3的表达不仅在转移性肿瘤中大幅增加，而且在一部分可能随后发生转移的原发性肿瘤中也显著升高。原发性局限性肿瘤未表达IMP3的患者比表达IMP3的患者具有更长的无转移生存期和总生存期（p<0.0001）。IMP3阳性局限性肿瘤患者的5年无转移生存率远低于IMP3阴性肿瘤患者（I期肿瘤，44%对98%，风险比17.18[95%CI 7.82 - 37.78]；II期，41%对94%，10.14[3.46 - 29.68]；III期，16%对62%，4.04[2.23 - 7.31]）。IMP3表达还与5年总生存期降低相关（I期，32%对89%，6.44[3.63 - 11.42]；II期，41%对88%，6.93[2.63 - 18.27]；III期，14%对58%，3.46[1.98 - 6.05]）。对原发性肿瘤中IMP3状态（阳性对阴性）的多变量分析显示，无转移生存期的风险比为5.84（95%CI 3.60 - 9.49），总生存期的风险比为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。
解读
IMP3是一种独立的预后标志物，可在肾细胞癌初诊时用于识别具有高转移潜能且可能从早期全身治疗中获益的患者。
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