Androgen receptor (AR) signaling is essential for prostate cancer (PC) progression and treatment. Experiments have demonstrated that the intratumoral androgen levels are not affected by circulating androgen levels, but rather modulated by local steroid-converting enzyme activities. The expression modulation status of human steroid-converting enzymes and nuclear receptors are of great promise to identify novel therapeutic targets. Meta-analysis was performed with 9 cohorts (1093 specimens) from Gene Expression Omnibus, 16 cohorts (933 specimens) from Oncomine and the TCGA cohort (550 specimens). We found significant up regulation of 5α-reductase type 1 and type 3 in both primary and metastatic PC, together with the down regulation of AKR1C2 in primary PC, contributing to the high intratumoral DHT levels. The expression of AR in metastatic PC was up regulated, indicating the importance of AR signaling in the progression of this cancer. The down regulations of HSD11B1 and NR3C1 in primary and metastatic PC may diminish the anti-inflammation and anti-proliferation effects of glucocorticoids signaling. Furthermore, the decrease of progesterone receptor (PGR) expression in primary and metastatic PC was also observed, relieving the suppression effect of PGR on PC proliferation. The clinical evidences of the remarkable expression modulation of steroid-converting enzymes and receptors in PC may indicate novel combined treatment against this highly incident cancer.

中文翻译：

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前列腺癌中类固醇转化酶和相关受体的荟萃分析提示了新的联合疗法。

雄激素受体（AR）信号对于前列腺癌（PC）的进展和治疗至关重要。实验表明，肿瘤内雄激素水平不受循环雄激素水平的影响，而是受到局部类固醇转化酶活性的调节。人类类固醇转化酶和核受体的表达调节状态对于鉴定新的治疗靶标具有很大的希望。使用来自Gene Expression Omnibus的9个队列（1093个样本），来自Oncomine的16个队列（933个样本）和TCGA队列（550个样本）进行荟萃分析。我们发现在原发性和转移性PC中5α-还原酶1型和3型的显着上调，以及原发性PC中AKR1C2的下调，导致高的肿瘤内DHT水平。转移性PC中AR的表达上调，表明AR信号在这种癌症进展中的重要性。HSD11B1和NR3C1在原发性和转移性PC中的下调可能减弱了糖皮质激素信号传导的抗炎和抗增殖作用。此外，还观察到原发性和转移性PC中孕激素受体（PGR）表达的减少，从而减轻了PGR对PC增殖的抑制作用。PC中类固醇转化酶和受体的显着表达调节的临床证据可能表明，针对这种高发病率癌症的新型联合治疗。HSD11B1和NR3C1在原发性和转移性PC中的下调可能减弱了糖皮质激素信号传导的抗炎和抗增殖作用。此外，还观察到原发性和转移性PC中孕激素受体（PGR）表达的减少，从而减轻了PGR对PC增殖的抑制作用。PC中类固醇转化酶和受体的显着表达调节的临床证据可能表明，针对这种高发病率癌症的新型联合治疗。HSD11B1和NR3C1在原发性和转移性PC中的下调可能减弱了糖皮质激素信号传导的抗炎和抗增殖作用。此外，还观察到原发性和转移性PC中孕激素受体（PGR）表达的减少，从而减轻了PGR对PC增殖的抑制作用。PC中类固醇转化酶和受体的显着表达调节的临床证据可能表明，针对这种高发病率癌症的新型联合治疗。