College of Life Sciences, Yantai University, 30th Qingquan Road, 264005, Yantai, Shandong Province, China.
School of Life Sciences, Sun Yat-sen University, 510275, Guangzhou, Guangdong Province, China.
BMC Urol. 2022 Oct 18;22(1):162. doi: 10.1186/s12894-022-01113-5.
Prostate cancer (PCa) is one of the most diagnosed cancers in the world. PCa inevitably progresses to castration-resistant prostate cancer (CRPC) after androgen deprivation therapy treatment, and castration-resistant state means a shorter survival time than other causes. Here we aimed to define castration-dependent and -independent diver genes and molecular pathways in CRPC which are responsible for such lethal metastatic events.
By employing digital gene expression (DGE) profiling, the alterations of the epididymal gene expression profile in the mature and bilateral castrated rat were explored. Then we detect and characterize the castration-dependent and -independent genes and pathways with two data set of CPRC-associated gene expression profiles publicly available on the NCBI.
We identified 1,632 up-regulated and 816 down-regulated genes in rat's epididymis after bilateral castration. Differential expression analysis of CRPC samples compared with the primary PCa samples was also done. In contrast to castration, we identified 97 up-regulated genes and 128 down-regulated genes that changed in both GEO dataset and DGE profile, and 120 up-regulated genes and 136 down-regulated genes changed only in CRPC, considered as CRPC-specific genes independent of castration. CRPC-specific DEGs were mainly enriched in cell proliferation, while CRPC-castration genes were associated with prostate gland development. NUSAP1 and NCAPG were identified as key genes, which might be promising biomarkers of the diagnosis and prognosis of CRPC.
Our study will provide insights into gene regulation of CRPC dependent or independent of castration and will improve understandings of CRPC development and progression.
前列腺癌（PCa）是世界上最常见的癌症之一。在雄激素剥夺治疗后，PCa 不可避免地进展为去势抵抗性前列腺癌（CRPC），而去势抵抗状态意味着比其他原因存活时间更短。在这里，我们旨在定义 CRPC 中依赖和不依赖去势的 diver 基因和分子途径，这些基因和分子途径负责导致这种致命的转移事件。
通过采用数字基因表达（DGE）谱分析，探索成熟和双侧去势大鼠附睾基因表达谱的变化。然后，我们利用两个公开的 NCBI 上的与 CRPC 相关的基因表达谱数据集，检测和表征依赖去势和不依赖去势的基因和途径。
我们在大鼠附睾中鉴定出 1632 个上调和 816 个下调基因。还对 CRPC 样本与原发性 PCa 样本进行了差异表达分析。与去势相比，我们在 GEO 数据集和 DGE 图谱中鉴定出 97 个上调基因和 128 个下调基因发生变化，而在 CRPC 中仅鉴定出 120 个上调基因和 136 个下调基因发生变化，这些基因被认为是不依赖于去势的 CRPC 特异性基因。CRPC 特异性差异表达基因主要富集在细胞增殖中，而 CRPC-去势基因与前列腺发育有关。NUSAP1 和 NCAPG 被鉴定为关键基因，它们可能是 CRPC 诊断和预后的有前途的生物标志物。
我们的研究将深入了解 CRPC 依赖或不依赖去势的基因调控，并将提高对 CRPC 发展和进展的认识。
