Elevated osteonectin/SPARC expression in primary prostate cancer predicts metastatic progression
Elevated osteonectin/SPARC expression in primary prostate cancer predicts metastatic progression
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DOI：
10.1038/pcan.2011.61
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发表时间：
2012-06-01
影响因子：
4.8
通讯作者：
Petrovics, G.
中科院分区：
文献类型：
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作者：
DeRosa, C. A.;Furusato, B.;Petrovics, G.
背景：大多数前列腺癌（CaP）是在早期发现的，预后不确定。因此，人们正在大力努力定义具有侵袭性进展特征的 CaP 早期预测标志物。 方法：为了定义此类预后标志物，我们对根治性前列腺切除术后平均随访 78 个月的患者 (N = 40) 原发性肿瘤的高分化 (PD) 肿瘤细胞的转录组进行了比较分析。在来自独立患者队列的原发性肿瘤中，通过定量实时逆转录酶 PCR (RT-PCR) (N = 110) 在转录水平上进行验证实验，并通过免疫组织化学在蛋白质水平上进行验证实验 (N = 53)。 结果：以 SPARC 基因作为中心节点的 12 个基因的生化网络的关联通过 PD 表型突出显示。值得注意的是，该网络中基因启动子中的 NKXH_NKXH_HOX 复合调控元件显着富集，表明这种基因表达调控机制在 CaP 进展中具有生物学意义。此外，对 110 名患者的原发性前列腺肿瘤细胞中 SPARC mRNA 的定量表达分析验证了 SPARC 表达与分化不良和较高的格里森评分之间的关联。最显着的是，前列腺切除术时较高的 SPARC 蛋白表达与随后的转移发展相关（P = 0.0006，AUC = 0.803）。 结论：总之，我们认为原发性 CaP 中 SPARC 的评估有潜力作为转移进展的预后标志物。
BACKGROUND: The majority of prostate cancers (CaP) are detected in early stages with uncertain prognosis. Therefore, an intensive effort is underway to define early predictive markers of CaP with aggressive progression characteristics.METHODS: In order to define such prognostic markers, we performed comparative analyses of transcriptomes of well-and poorly differentiated (PD) tumor cells from primary tumors of patients (N = 40) with 78 months of mean follow-up after radical prostatectomy. Validation experiments were carried out at transcript level by quantitative real-time reverse transcriptase-PCR (RT-PCR) (N = 110) and at protein level by immunohistochemistry (N = 53) in primary tumors from an independent patient cohort.RESULTS: Association of a biochemical network of 12 genes with SPARC gene as a central node was highlighted with PD phenotype. Of note, there was remarkable enrichment of NKXH_NKXH_HOX composite regulatory elements in the promoter of the genes in this network suggesting a biological significance of this gene-expression regulatory mechanism in CaP progression. Further, quantitative expression analyses of SPARC mRNA in primary prostate tumor cells of 110 patients validated the association of SPARC expression with poor differentiation and higher Gleason score. Most significantly, higher SPARC protein expression at the time of prostatectomy was associated with the subsequent development of metastasis (P = 0.0006, AUC = 0.803).CONCLUSIONS: In summary, we propose that evaluation of SPARC in primary CaP has potential as a prognostic marker of metastatic progression.