Expression signatures that correlated with Gleason score and relapse in prostate cancer
Expression signatures that correlated with Gleason score and relapse in prostate cancer
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DOI：
10.1016/j.ygeno.2007.02.005
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发表时间：
2007-06-01
期刊：
影响因子：
4.4
通讯作者：
Wang-Rodriguez, Jessica
中科院分区：
文献类型：
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作者：
Bibikova, Marina;Chudin, Eugene;Wang-Rodriguez, Jessica
当仅使用临床和病理标准时，预测前列腺癌的预后仍然是一个挑战。我们使用基于阵列的DASL检测，通过512个优先基因的基因表达谱来识别预测福尔马林固定、石蜡包埋（FFPE）前列腺癌复发的分子特征。在我们分析的71例患者中，除3例外，所有患者在根治性乳腺癌切除术后均无残留肿瘤（定义为阴性手术切缘），无患者在手术后接受辅助治疗。所有71例患者在根治性前列腺切除术后血清PSA均检测不到。随访期为44 ± 15个月。用这些样品获得了高度可重复的基因表达模式（平均R-2=0.99）。我们确定了一组与Gleason分级正相关的11个基因和负相关的5个基因。基因表达评分（格克斯）源自16个基因的表达水平。我们评估了这些基因的预后价值，发现格克斯与疾病复发显著相关（p=0.007）。这些结果表明，我们使用的方法对于异质FFPE组织中的表达谱分析对于癌症诊断/预后生物标志物发现和验证是有效的。(c)2007爱思唯尔公司All rights reserved.
Predicting prognosis in prostate carcinoma remains a challenge when using clinical and pathologic criteria only. We used an array-based DASL assay to identify molecular signatures for predicting prostate cancer relapse in formalin-fixed, paraffin-embedded (FFPE) prostate cancers, through gene expression profiling of 512 prioritized genes. Of the 71 patients that we analyzed, all but 3 had no evidence of residual tumor (defined as negative surgical margins) following radical prostatectomy and no patient received adjuvant therapy following surgery. All of the 71 patients had an undetectable serum PSA following radical prostatectomy. Follow-up period was 44 +/- 15 months. Highly reproducible gene expression patterns were obtained with these samples (average R-2=0.99). We identified a panel of 11 genes that correlated positively and 5 genes that correlated negatively with Gleason grade. A gene expression score (GEX) was derived from the expression levels of the 16 genes. We assessed the prognostic value of these genes and found the GEX significantly correlated with disease relapse (p=0.007). These results suggest that the approach we used is effective for expression profiling in heterogeneous FFPE tissues for cancer diagnosis/prognosis biomarker discovery and validation. (c) 2007 Elsevier Inc. All rights reserved.