前列腺癌（PCa）是全球最常见的癌症之一，因此识别潜在的预后生物标志物至关重要。本研究收集了来自癌症蛋白质组图谱（TCPA）和癌症基因组图谱（TCGA）的344例PCa病例的生存信息、基因表达和蛋白质表达数据，以研究潜在的预后生物标志物。机器学习算法基于每个患者的风险评分构建了综合预后相关蛋白质（IPRPs）模型。IPRPs模型表明，升高的RAD50表达（p = 0.016）和下调的SMAD4表达（p = 0.017）与PCa患者的不良预后显著相关。免疫组化（IHC）染色和Western blot（WB）分析揭示了验证队列中肿瘤和正常组织之间SMAD4和RAD50蛋白质的显着差异表达。根据整体的IHC评分，在验证队列中，SMAD4低表达（p < 0.0001）和RAD50高表达（p = 0.0001）与不良结果显着相关。此外，SMAD4的表达与大多数免疫检查点分子呈显著负相关，在验证队列中，SMAD4低表达组与高SMAD4表达组相比，L A G3（p ＜ 0.05）、TGFβ（p ＜ 0.001）和PD-L1（p ＜ 0.05）的水平显着升高。 SMAD4表达低的患者具有记忆B细胞（p = 0.002）、CD8 + T细胞（p ＜ 0.001）、调节性T细胞（p = 0.006）、M2型巨噬细胞（p ＜ 0.001）的显着高浸润，并具有天然B细胞（p = 0.002）、浆细胞（p ＜ 0.001）、休眠的记忆CD4 + T细胞（p ＜ 0.001）和嗜酸性粒细胞（p = 0.045）的显着低浸润。候选蛋白质主要涉及抗原处理和呈递、干细胞分化和I型干扰素途径。在线版本包含补充材料，可在 10.1007/s43657-022-00070-1 上获得。©2022国际人类表型研究所（上海），Springer Nature或其许可方在与作者或其他权利所有人订立的出版协议下对本文拥有独占权利3自行归档本文的已接受手稿版本仅受此类出版协议和适用法律的规定约束。

As prostate cancer (PCa) is one of the most commonly diagnosed cancer worldwide, identifying potential prognostic biomarkers is crucial. In this study, the survival information, gene expression, and protein expression data of 344 PCa cases were collected from the Cancer Proteome Atlas (TCPA) and the Cancer Genome Atlas (TCGA) to investigate the potential prognostic biomarkers. The integrated prognosis-related proteins (IPRPs) model was constructed based on the risk score of each patients using machine-learning algorithm. IPRPs model suggested that Elevated RAD50 expression (p = 0.016) and down-regulated SMAD4 expression (p = 0.017) were significantly correlated with unfavorable outcomes for PCa patients. Immunohistochemical (IHC) staining and western blot (WB) analysis revealed significant differential expression of SMAD4 and RAD50 protein between tumor and normal tissues in validation cohort. According to the overall IHC score, patients with low SMAD4 (p < 0.0001) expression and high RAD50 expression (p = 0.0001) were significantly correlated with poor outcomes. Besides, expression of SMAD4 showed significantly negative correlation with most immune checkpoint molecules, and the low SMAD4 expression group exhibited significantly high levels of LAG3 (p < 0.05), TGFβ (p < 0.001), and PD-L1 (p < 0.05) compared with the high SMAD4 expression group in the validation cohort. Patients with low SMAD4 expression had significantly higher infiltration of memory B cells (p = 0.002), CD8 + T cells (p < 0.001), regulatory T cells (p = 0.006), M2-type macrophages (p < 0.001), and significantly lower infiltration of naïve B cells (p = 0.002), plasma cells (p < 0.001), resting memory CD4 + T cells (p < 0.001) and eosinophils (p = 0.045). Candidate proteins were mainly involved in antigen processing and presentation, stem cell differentiation, and type I interferon pathways.The online version contains supplementary material available at 10.1007/s43657-022-00070-1.© International Human Phenome Institutes (Shanghai) 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.