Smith Eric, Palethorpe Helen M, Ruszkiewicz Andrew R, Edwards Suzanne, Leach Damien A, Underwood Tim J, Need Eleanor F, Drew Paul A
Dig Dis Sci. 2016 Feb;61(2):433-43. doi: 10.1007/s10620-015-3909-0.
Esophageal adenocarcinoma is a male-dominant disease, but the role of androgens is unclear.
To examine the expression and clinical correlates of the androgen receptor (AR) and the androgen-responsive gene FK506-binding protein 5 (FKBP5) in esophageal adenocarcinoma.
Expression of AR and FKBP5 was determined by immunohistochemistry. The effect of the AR ligand 5α-dihydrotestosterone (DHT) on the expression of a panel of androgen-responsive genes was measured in AR-positive and AR-negative esophageal adenocarcinoma cell lines. Correlations in expression between androgen-responsive genes were analyzed in an independent cohort of esophageal adenocarcinoma tissues.
There was AR staining in 75 of 77 cases (97 %), and FKBP5 staining in 49 (64 %), all of which had nuclear AR. Nuclear AR with FKBP5 expression was associated with decreased median survival (451 vs. 2800 days) and was an independent prognostic indicator (HR 2.894, 95 % CI 1.396–6.002, p = 0.0043) in multivariable Cox proportional hazards models. DHT induced a significant increase in expression of the androgen-responsive genes FKBP5, HMOX1, FBXO32, VEGFA, WNT5A, and KLK3 only in AR-positive cells in vitro. Significant correlations in expression were observed between these androgen-responsive genes in an independent cohort of esophageal adenocarcinoma tissues.
Nuclear AR and expression of FKBP5 is associated with decreased survival in esophageal adenocarcinoma.
食管腺癌是一种男性主导的疾病，但雄激素的作用尚不清楚。
研究雄激素受体（AR）和雄激素反应基因FK506结合蛋白5（FKBP5）在食管腺癌中的表达及其临床相关性。
采用免疫组织化学法检测AR和FKBP5的表达。在AR阳性和AR阴性的食管腺癌细胞系中，检测AR配体5α-双氢睾酮（DHT）对一组雄激素反应基因表达的影响。在一组独立的食管腺癌组织中分析雄激素反应基因表达之间的相关性。
77例中有75例（97%）存在AR染色，49例（64%）存在FKBP5染色，所有病例均有核AR。核AR与FKBP5表达与中位生存期降低相关（451天对2800天），并且在多变量Cox比例风险模型中是一个独立的预后指标（风险比2.894，95%可信区间1.396 - 6.002，p = 0.0043）。DHT仅在体外AR阳性细胞中显著诱导雄激素反应基因FKBP5、HMOX1、FBXO32、VEGFA、WNT5A和KLK3的表达增加。在一组独立的食管腺癌组织中，观察到这些雄激素反应基因之间存在显著的表达相关性。
核AR和FKBP5的表达与食管腺癌患者生存率降低相关。
