體壇抗性前列腺癌（CRPC）代表了一種具有1-2年中位生存時間的進階前列腺癌（PCa）。目前，由於對CRPC特定腫瘤微環境（TME）特徵的知識有限，缺乏可靠的基因面板來預測激素治療（HT）效應。在本研究中，我們首先利用從TCGA在線數據庫檢索得到的批量测序數據篩選CRPC樣本中的上調基因，並進一步在下載的四組單細胞RNA测序（scRNAseq）數據中研究這些基因的表達狀態：GSE117403 包含16個正常人前列腺樣本；GSE141445 包含13個前列腺癌樣本；GSE176031 包含11個前列腺癌樣本和GSE137829 包含6個CRPC樣本。我們確定了一系列CRPC特定的TME特徵，包括富含PEG10+神經內分泌細胞的數量增加，腫瘤細胞中PPIB/CCDC74A/GAPDH/AR基因的表達增加，癌相關成纖維細胞（CAFs）中FAP/TGFB1表達的增加，免疫環境受抑制，表現增強的M2巨噬細胞極化，T細胞筋疲力盡以及調節性B細胞數量增加。我們進一步利用這些特徵建立了一個包含12個基因的面板，並顯示該面板能夠將CRPC樣本與PCa樣本區分開來（AUC為0.78），並且具有更高面板得分的CRPC患者更容易發生治療失敗或進展（R = -0.47，p = 0.019）。基於CRPC的這些獨特TME特徵，我們建立了一個用於估計PCa治療中HT效應持續時間的預測工具。我們的結果揭示了前列腺癌變得抗去勢性的機制。應考慮進一步研究PEG10（和/或其他基因）以評估治療效果。

Castration-resistant prostate cancer (CRPC) represents one type of advanced prostate cancer (PCa) with a median survival time of 1-2 years. Currently, there is a lack of reliable gene panels in predicting hormone treatment (HT) responses due to limited knowledge of CRPC-specific tumor-microenvironment (TME) characteristics.In this study, we first screened for up-regulated genes in CRPC samples using bulk-sequencing data retrieved from TCGA online database, and further investigated the expression status of these genes in four sets of downloaded single-cell RNA sequencing (scRNAseq) data: GSE117403 containing 16 normal human prostate samples; GSE141445 containing 13 PCa samples; GSE176031 containing 11 PCa samples and GSE137829 containing 6 CRPC samples.We identified a series of CRPC-specific TME characteristics including an enriched number of PEG10+ neuroendocrine cells, elevated expression of PPIB/CCDC74A/GAPDH/AR genes in tumor cells, increased expression of FAP/TGFB1 in cancer-associated fibroblasts (CAFs), suppressed immune environment featured by enhanced M2 macrophage polarization, T cell exhaustion and increased number of regulatory B cells. We further established a 12-gene panel using these characteristics and showed that this panel could separate CRPC samples from PCa samples (AUC of 0.78), and CRPC patients with higher panel scores tended to have treatment failure or progression (R = -0.47, p = 0.019).Based on these unique TME characteristics of CRPC, we established a prediction tool for estimating the duration of HT responses in PCa treatment. Our results suggest mechanisms by which prostate cancer becomes castrate resistant. Further study of PEG10 (and/or others) to evaluate therapeutic efficacy should be considered.