Institut de Génomique Fonctionnelle de Lyon (IGFL), Université de Lyon, CNRS UMR5242, INRA1288, Ecole Normale Supérieure de Lyon, Lyon, France.
PLoS One. 2013 Jun 28;8(6):e66278. doi: 10.1371/journal.pone.0066278. Print 2013.
Several data favor androgen receptor implication in prostate cancer initiation through the induction of several gene activation programs. The aim of the study is to identify potential biomarkers for early diagnosis of prostate cancer (PCa) among androgen-regulated genes (ARG) and to evaluate comparative expression of these genes in normal prostate and normal prostate-related androgen-sensitive tissues that do not (or rarely) give rise to cancer.
ARG were selected in non-neoplastic adult human prostatic epithelial RWPE-1 cells stably expressing an exogenous human androgen receptor, using RNA-microarrays and validation by qRT-PCR. Expression of 48 preselected genes was quantified in tissue samples (seminal vesicles, prostate transitional zones and prostate cancers, benign prostatic hypertrophy obtained from surgical specimens) using TaqMan® low-density arrays. The diagnostic performances of these potential biomarkers were compared to that of genes known to be associated with PCa (i.e. PCA3 and DLX1).
By crossing expression studies in 26 matched PCa and normal prostate transitional zone samples, and 35 matched seminal vesicle and PCa samples, 14 genes were identified. Similarly, 9 genes were overexpressed in 15 benign prostatic hypertrophy samples, as compared to PCa samples. Overall, we selected 8 genes of interest to evaluate their diagnostic performances in comparison with that of PCA3 and DLX1. Among them, 3 genes: CRYAB, KCNMA1 and SDPR, were overexpressed in all 3 reference non-cancerous tissues. The areas under ROC curves of these genes reached those of PCA3 (0.91) and DLX1 (0.94).
We identified ARG with reduced expression in PCa and with significant diagnostic values for discriminating between cancerous and non-cancerous prostatic tissues, similar that of PCA3. Given their expression pattern, they could be considered as potentially protective against prostate cancer. Moreover, they could be complementary to known genes overexpressed in PCa and included along with them in multiplex diagnostic tools.
多项数据表明，雄激素受体通过诱导多个基因激活程序参与前列腺癌的发生。本研究旨在从雄激素调控基因（ARG）中确定前列腺癌（PCa）早期诊断的潜在生物标志物，并评估这些基因在不（或很少）发生癌变的正常前列腺和正常前列腺相关雄激素敏感组织中的表达情况。
在稳定表达外源性人雄激素受体的非肿瘤性成人前列腺上皮 RWPE-1 细胞中，使用 RNA 微阵列和 qRT-PCR 进行验证，筛选 ARG。使用 TaqMan®低密度阵列定量分析组织样本（精液囊、前列腺移行区和前列腺癌、手术标本获得的良性前列腺增生）中 48 个预选基因的表达。将这些潜在生物标志物的诊断性能与已知与 PCa 相关的基因（即 PCA3 和 DLX1）进行比较。
通过对 26 对匹配的 PCa 和正常前列腺移行区样本以及 35 对匹配的精液囊和 PCa 样本的表达研究，鉴定出 14 个基因。同样，与 PCa 样本相比，在 15 个良性前列腺增生样本中，有 9 个基因表达上调。总的来说，我们选择了 8 个感兴趣的基因来评估它们的诊断性能，并与 PCA3 和 DLX1 进行比较。其中，3 个基因：CRYAB、KCNMA1 和 SDPR，在所有 3 种参考非癌组织中均表达上调。这些基因的 ROC 曲线下面积达到了 PCA3（0.91）和 DLX1（0.94）的水平。
我们鉴定出在 PCa 中表达下调的 ARG，并且具有显著的诊断价值，可以区分癌性和非癌性前列腺组织，与 PCA3 相似。鉴于它们的表达模式，它们可以被认为是潜在的前列腺癌保护因子。此外，它们可以与 PCa 中过度表达的已知基因互补，并与它们一起包含在多重诊断工具中。
