Expression and Cytoplasmic Localization of SAM68 Is a Significant and Independent Prognostic Marker for Renal Cell Carcinoma
Expression and Cytoplasmic Localization of SAM68 Is a Significant and Independent Prognostic Marker for Renal Cell Carcinoma
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SAM68 的表达和细胞质定位是肾细胞癌重要且独立的预后标志物
DOI：
10.1158/1055-9965.epi-09-0097
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发表时间：
2009-10-01
影响因子：
3.8
通讯作者：
Song, Libing
中科院分区：
文献类型：
--
作者：
Zhang, Zhiling;Li, Jun;Song, Libing
目的：本回顾性研究旨在探讨SAM68 （Src-associated in mitosis, 68 kDa）在大量肾癌手术标本中的表达和定位及其与肾癌进展的关系。实验设计：采用逆转录- pcr和Western blot检测SAM68在正常肾小管上皮细胞、肾细胞癌细胞系以及9对肾细胞癌和匹配的肿瘤邻近肾组织中的蛋白和mRNA表达水平。采用免疫组织化学方法检测了241例临床病理特征的肾细胞癌样本中SAM68蛋白的表达和定位。通过统计分析检验预后和诊断相关性。结果：SAM68在肾细胞癌细胞系和肾细胞癌组织中均在转录和翻译水平上显著过表达。免疫组化分析显示，241例石蜡包埋肾细胞癌标本中129例（53.5%）SAM68蛋白高表达。SAM68表达与病理分期（P < 0.001）、T分型（P = 0.003）、N分型（P = 0.001）、M分型（P = 0.006）、Fuhrman分级（P < 0.001）有显著相关性。SAM68高表达的患者总生存期短于低表达的患者，且SAM68的胞质定位与临床病理分级及转归显著相关。多因素分析表明，SAM68蛋白过表达和细胞质定位是肾癌患者生存不良的独立预测因素。结论：我们的研究结果表明，SAM68可能是一种新的、有用的肾细胞癌预后标志物。在肾细胞癌患者中，SAM68的高表达和细胞质定位与较差的总生存率相关。（癌症流行病学杂志，2009;18(10):2685-93）
Purpose: This retrospective study aimed to examine the expression and localization of SAM68 (Src-associated in mitosis, 68 kDa) in a larger cohort of surgical specimens of renal cell carcinoma and their correlation with the progression of human renal cell carcinoma. Experimental Design: The protein and mRNA expression levels of SAM68 in normal renal tubular epithelial cells, renal cell carcinoma cell lines, as well as nine pairs of renal cell carcinoma and matched tumor-adjacent renal tissues were examined using reverse transcription-PCR and Western blot. Moreover, SAM68 protein expression and localization in 241 clinicopathologically characterized renal cell carcinoma samples were examined by immunohistochemistry. Prognostic and diagnostic associations were examined by statistical analyses. Results: SAM68 was markedly overexpressed in renal cell carcinoma cell lines and renal cell carcinoma tissues at both the transcriptional and translational levels. Immunohistochemical analysis revealed high SAM68 protein expression in 129 of the 241 (53.5%) paraffin-embedded archival renal cell carcinoma specimens. Moreover, there was a significant correlation between SAM68 expression and pathologic stage (P < 0.001), T classification (P = 0.003), N classification (P = 0.001), M classification (P = 0.006), and Fuhrman grade (P < 0.001). Patients with higher SAM68 expression had shorter overall survival time than patients with lower SAM68 expression, and the cytoplasmic localization of SAM68 significantly correlated with clinicopathologic grade and outcome. Multivariate analysis indicated that SAM68 protein overexpression and cytoplasmic localization were independent predictors for poor survival of renal cell carcinoma patients. Conclusions: Our results suggest that SAM68 could represent a novel and useful prognostic marker for renal cell carcinoma. High SAM68 expression and cytoplasmic localization are associated with poor overall survival in renal cell carcinoma patients. (Cancer Epidemiol Biomarkers Prev 2009;18(10):2685–93)