Expression of adipose differentiation-related protein: A predictor of cancer-specific survival in clear cell renal carcinoma
Expression of adipose differentiation-related protein: A predictor of cancer-specific survival in clear cell renal carcinoma
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DOI：
10.1158/1078-0432.ccr-06-1877
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发表时间：
2007-01-01
影响因子：
11.5
通讯作者：
Kubota, Yoshinobu
中科院分区：
文献类型：
--
作者：
Yao, Masahiro;Huang, Ying;Kubota, Yoshinobu
目的：我们最近发现脂肪分化相关蛋白（ADFP）是透明细胞亚型肾细胞癌（RCC）的潜在诊断和预后生物标志物。为了进一步评估ADFP表达水平与临床病理特征和患者预后之间的相关性，我们对透明细胞RCC患者进行了回顾性研究。实验设计：在1986年3月至2004年6月期间，432例连续的散发性透明细胞肾细胞癌患者接受了肾切除术。实时荧光定量PCR检测原发肿瘤和18例转移瘤中ADFP的表达水平。收集临床病理和预后资料，以及选定病例的von Hippel-Lindau病（VHL）基因改变状况。结果：在没有症状表现的病例中，以及在低阶段、低级别或VHL改变阳性的透明细胞RCC中，ADFP的表达明显较高，而在具有纺锤形/多形性成分或转移性病变的未分化肿瘤中，ADFP的表达则下调。单因素分析显示，高ADFP表达与更好的癌症特异性生存和无癌症生存相关。进一步的Cox多变量分析结合分裂样本验证方法表明，在所有肿瘤分期和晚期转移病例中，ADFP表达仍然是癌症特异性生存的独立预测因子，而ADFP表达对癌症复发的预测价值相当弱。结论：ADFP的表达可能反映了肿瘤的分化状态，检测其表达水平可为透明细胞RCC患者的肿瘤特异性生存提供有用的预后信息。
Purpose: We recently found that adipose differentiation-related protein (ADFP) is a potential diagnostic and prognostic biomarker for clear cell subtype renal cell carcinoma (RCC). To further evaluate the correlation between ADFP expression levels and clinicopathologic characteristics and patient outcome, we retrospectively examined patients with clear cell RCC.Experimental Design: A series of 432 consecutive patients with sporadic clear cell RCC who underwent nephrectomy between March 1986 and June 2004 were enrolled in the study. ADFP expression levels in the primary tumors and in 18 metastases were measured by real-time quantitative PCR. The clinicopathologic and prognostic data were collected, as well as the von Hippel-Lindau disease (VHL) gene alteration status in selected cases.Results: ADFP expression was apparently high in cases without a symptomatic presentation, as well as in cases of low-stage, low-grade, or VHL alteration-positive clear cell RCC, whereas it was down-regulated in undifferentiated tumors with a spindle/pleomorphic component or metastatic lesions. Univariate analyses showed that high ADFP expression was associated with better cancer-specific survival and cancer-free survival. Further Cox multivariate analyses combined with the split-sample validation method showed that ADFP expression still remains an independent predictor for cancer-specific survival in all tumor stages and in advanced metastatic cases, whereas the predictive value of ADFP expression for cancer recurrence is rather weak.Conclusions: The ADFP expression may represent the tumor differentiation status, and the detection of the expression levels provides useful prognostic information for cancer-specific survival in patients with clear cell RCC.