Surgical intervention for symptomatic benign prostatic hyperplasia is correlated with expression of the AP-1 transcription factor network.
Surgical intervention for symptomatic benign prostatic hyperplasia is correlated with expression of the AP-1 transcription factor network.
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DOI：
10.1002/pros.22785
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发表时间：
2014-05
期刊：
影响因子：
2.8
通讯作者：
Strand, Douglas W.
中科院分区：
文献类型：
--
作者：
Lin-Tsai, Opal;Clark, Peter E.;Miller, Nicole L.;Fowke, Jay H.;Hameed, Omar;Hayward, Simon W.;Strand, Douglas W.
关键词：
大约三分之一的患者治疗失败的良性前列腺增生和相关的下尿路症状（BPH/LUTS）需要手术干预。我们的目的是为接受LUTS手术干预的患者建立分子特征，以解决治疗缺陷。对26例接受手术治疗严重LUTS的患者进行临床、分子和组织病理学分析。从37例轻度症状行根治性前列腺切除术的患者中分离出偶发过渡带结节。收集年龄、前列腺体积、用药、前列腺特异性抗原、症状评分、体重指数、糖尿病发病率等临床参数。采用多变量逻辑回归分析，对潜在的混杂变量进行调整，以检查患者临床特征与通过分子谱分析确定的分子靶点之间的关系。与偶发性前列腺增生相比，进行性症状性前列腺增生与激活蛋白-1转录因子/趋化因子网络的表达增加有关。正如预期的那样，雄激素受体水平与年龄呈负相关，5α-还原酶抑制剂（5ARI）治疗与组织前列腺特异性抗原水平呈负相关；然而，在5ARI治疗和c-FOS表达增加之间也发现了一种新的关联。这项研究提供了分子证据，表明促炎激活蛋白-1转录因子网络和相关趋化因子在症状性前列腺疾病中高度富集，这一特征与许多其他慢性自身免疫性疾病具有分子分类。由于5ARI治疗与c-FOS表达增加相关，未来的研究应探讨活化蛋白-1蛋白的增加是否是症状性前列腺疾病、炎症或对传统激素治疗产生抵抗的原因。
Approximately one-third of patients fail medical treatment for benign prostatic hyperplasia and associated lower urinary tract symptoms (BPH/LUTS) requiring surgical intervention. Our purpose was to establish a molecular characterization for patients undergoing surgical intervention for LUTS to address therapeutic deficiencies. Clinical, molecular, and histopathological profiles were analyzed in 26 patients undergoing surgery for severe LUTS. Incidental transitional zone nodules were isolated from 37 patients with mild symptoms undergoing radical prostatectomy. Clinical parameters including age, prostate volume, medication, prostate specific antigen, symptom score, body mass index, and incidence of diabetes were collected. Multivariate logistic regression analysis with adjustments for potential confounding variables was used to examine associations between patient clinical characteristics and molecular targets identified through molecular profiling. Compared to incidental BPH, progressive symptomatic BPH was associated with increased expression of the activating protein-1 transcription factor/chemokine network. As expected, inverse correlations were drawn between androgen receptor levels and age, as well as between 5α-reductase inhibitor (5ARI) treatment and tissue prostate specific antigen levels; however, a novel association was also drawn between 5ARI treatment and increased c-FOS expression. This study provides molecular evidence that a network of pro-inflammatory activating protein-1 transcription factors and associated chemokines are highly enriched in symptomatic prostate disease, a profile that molecularly categorizes with many other chronic autoimmune diseases. Because 5ARI treatment was associated with increased c-FOS expression, future studies should explore whether increased activating protein-1 proteins are causal factors in the development of symptomatic prostate disease, inflammation or resistance to traditional hormonal therapy.
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