Kempkensteffen Carsten, Hinz Stefan, Christoph Frank, Köllermann Jens, Krause Hans, Schrader Mark, Schostak Martin, Miller Kurt, Weikert Steffen
Department of Urology, Charité-Campus Benjamin Franklin, Universitätsmedizin Berlin, Berlin, Germany.
Int J Cancer. 2007 Mar 1;120(5):1081-6. doi: 10.1002/ijc.22416.
The expression of the inhibitor of apoptosis (IAP) family members cIAP1 and cIAP2 have been shown to be altered in various cancer entities. This study was done to characterize the tumor-related expression profile of cIAP1 and cIAP2 in patients with renal cell carcinomas (RCC) and to evaluate its potential predictive value after curative resection. Expression of cIAP1 and cIAP2 was analyzed by real-time RT-PCR in RCC and corresponding normal tissue samples obtained from a cohort of 127 RCC patients (median follow-up: 48 months) undergoing surgical treatment. Expression data was correlated to histopathological variables and outcome. Overexpression of cIAP1 and cIAP2 occurred in most RCC specimens (p < 0.001), but 20% of the patients had lower cIAP levels in malignant than in normal tissue. The cIAP1 expression correlated with the tumor stage, levels being higher in pT1 tumors than in advanced pathological stages (p = 0.002). Decreased cIAP1 expression in RCC relative to paired normal samples predicted an abbreviated time to recurrence (hazard rate 2.96; 95% CI: 1.23-7.09) and tumor-specific survival (hazard rate 2.78; 95% CI: 1.22-6.38) irrespective of the tumor stage and grade. The prognostic effect of cIAP1 was most pronounced in patients with pT3 disease (log rank test p = 0.001). The results of uni- and multivariate analysis suggest a prognostic value of cIAP1 expression for RCC patients, downregulation indicating an aggressive, potentially lethal phenotype.
凋亡抑制蛋白（IAP）家族成员cIAP1和cIAP2的表达已被证实在多种癌症实体中发生改变。本研究旨在描述肾细胞癌（RCC）患者中cIAP1和cIAP2的肿瘤相关表达谱，并评估其在根治性切除术后的潜在预测价值。通过实时逆转录聚合酶链反应（RT-PCR）分析了127例接受手术治疗的RCC患者（中位随访时间：48个月）的RCC及相应正常组织样本中cIAP1和cIAP2的表达。将表达数据与组织病理学变量和预后相关联。大多数RCC标本中存在cIAP1和cIAP2的过表达（p<0.001），但20%的患者恶性组织中的cIAP水平低于正常组织。cIAP1表达与肿瘤分期相关，pT1期肿瘤中的水平高于晚期病理分期（p = 0.002）。相对于配对的正常样本，RCC中cIAP1表达降低预示着复发时间缩短（风险率2.96；95%置信区间：1.23 - 7.09）和肿瘤特异性生存时间缩短（风险率2.78；95%置信区间：1.22 - 6.38），与肿瘤分期和分级无关。cIAP1的预后作用在pT3期疾病患者中最为明显（对数秩检验p = 0.001）。单因素和多因素分析结果表明，cIAP1表达对RCC患者具有预后价值，其下调表明具有侵袭性、潜在致死性的表型。
