Lane Brian R, Li Jianbo, Zhou Ming, Babineau Denise, Faber Pieter, Novick Andrew C, Williams Bryan R G
Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, Ohio 44195, USA.
J Urol. 2009 Feb;181(2):849-60. doi: 10.1016/j.juro.2008.10.069. Epub 2008 Dec 17.
Gene expression profiling has been shown to provide prognostic information on patients with solitary sporadic renal cell carcinoma. To our knowledge there is no reliable way to differentiate synchronous renal metastasis from bilateral primary tumors in patients with bilateral renal cell carcinoma. We present data using a custom kidney cancer cDNA array that can predict the outcome in patients with unilateral and bilateral renal cell carcinoma.
Fresh frozen tissue from 38 clear cell renal cell carcinomas was analyzed using a cancer cDNA array containing 3,966 genes relevant to cancer or kidney development. Median followup was 5.3 years. Cancer recurred in 12 patients (43%) and 11 (39%) had died by the last followup.
Using a training data set of 8 tumors a 44 gene expression profile distinguishing aggressive and indolent clear cell renal cell carcinoma was identified. Of 29 single clear cell renal cell carcinomas 16 and 13 were predicted to be indolent and aggressive, respectively, by the gene expression profile. Recurrence-free survival at 5 years was 68% and 42% in these 2 groups, respectively (p = 0.032). Clear cell renal cell carcinoma classified as indolent or aggressive according to SSIGN (stage, size, grade and necrosis) score showed a 5-year recurrence-free survival rate of 78% and 42%, respectively (p = 0.021). On Cox proportional hazards analysis the gene expression profile was not an independent predictor of recurrence-free survival after accounting for SSIGN score. Gene expression profile classification correlated with cancer specific survival at 5 years in 4 of 4 patients with metachronous clear cell renal cell carcinoma but in only 2 of 4 with bilateral synchronous clear cell renal cell carcinoma.
Gene expression profiling using a kidney cancer relevant cDNA array can differentiate between aggressive and indolent clear cell renal cell carcinomas. Gene expression profile results may be most useful for unilateral clear cell renal cell carcinoma when results are discordant with predictions of tumor behavior based on standard clinicopathological features. In addition, gene expression profiling can provide prognostic information that may help characterize tumors of unknown clinical stage, such as bilateral metachronous clear cell renal cell carcinoma.
基因表达谱分析已被证明可为散发性孤立性肾细胞癌患者提供预后信息。据我们所知，对于双侧肾细胞癌患者，尚无可靠方法区分同步性肾转移与双侧原发性肿瘤。我们展示了使用定制肾癌cDNA阵列的数据，该阵列可预测单侧和双侧肾细胞癌患者的预后。
使用包含3966个与癌症或肾脏发育相关基因的癌症cDNA阵列，对38例透明细胞肾细胞癌的新鲜冷冻组织进行分析。中位随访时间为5.3年。12例患者（43%）出现癌症复发，11例（39%）在最后一次随访时死亡。
利用8个肿瘤的训练数据集，确定了一个区分侵袭性和惰性透明细胞肾细胞癌的44基因表达谱。29例单发透明细胞肾细胞癌中，基因表达谱预测分别有16例和13例为惰性和侵袭性。这两组的5年无复发生存率分别为68%和42%（p = 0.032）。根据SSIGN（分期、大小、分级和坏死）评分分类为惰性或侵袭性的透明细胞肾细胞癌，其5年无复发生存率分别为78%和42%（p = 0.021）。在Cox比例风险分析中，在考虑SSIGN评分后，基因表达谱不是无复发生存的独立预测因素。4例异时性透明细胞肾细胞癌患者中有4例、而4例双侧同步性透明细胞肾细胞癌患者中只有2例的基因表达谱分类与5年癌症特异性生存相关。
使用与肾癌相关的cDNA阵列进行基因表达谱分析可区分侵袭性和惰性透明细胞肾细胞癌。当基因表达谱结果与基于标准临床病理特征的肿瘤行为预测不一致时，基因表达谱结果可能对单侧透明细胞肾细胞癌最为有用。此外，基因表达谱分析可提供预后信息，有助于对未知临床分期的肿瘤进行特征描述，如双侧异时性透明细胞肾细胞癌。
