大规模蛋白质组学数据揭示前列腺癌微环境中与预后相关的综合蛋白质特征以及SMAD4和RAD50在预后和免疫浸润中的作用。
Large-Scale Proteomics Data Reveal Integrated Prognosis-Related Protein Signatures and Role of SMAD4 and RAD50 in Prognosis and Immune Infiltrations of Prostate Cancer Microenvironment.
作者信息
Anwaier Aihetaimujiang, Zhu Shu-Xuan, Tian Xi, Xu Wen-Hao, Wang Yue, Palihati Maierdan, Wang Wei-Yue, Shi Guo-Hai, Qu Yuan-Yuan, Zhang Hai-Liang, Ye Ding-Wei
机构信息
Department of Urology, Fudan University Shanghai Cancer Center, No. 270 Dong'an Road, Shanghai, 200032 People's Republic of China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 20032 People's Republic of China.
出版信息
Phenomics. 2022 Sep 27;2(6):404-418. doi: 10.1007/s43657-022-00070-1. eCollection 2022 Dec.
UNLABELLED
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 expression ( = 0.016) and down-regulated expression ( = 0.017) were significantly correlated with unfavorable outcomes for PCa patients. Immunohistochemical (IHC) staining and western blot (WB) analysis revealed significant differential expression of and protein between tumor and normal tissues in validation cohort. According to the overall IHC score, patients with low ( < 0.0001) expression and high expression ( = 0.0001) were significantly correlated with poor outcomes. Besides, expression of showed significantly negative correlation with most immune checkpoint molecules, and the low expression group exhibited significantly high levels of ( < 0.05), ( < 0.001), and ( < 0.05) compared with the high expression group in the validation cohort. Patients with low expression had significantly higher infiltration of memory B cells ( = 0.002), CD8 + T cells ( < 0.001), regulatory T cells ( = 0.006), M2-type macrophages ( < 0.001), and significantly lower infiltration of naïve B cells ( = 0.002), plasma cells ( < 0.001), resting memory CD4 + T cells ( < 0.001) and eosinophils ( = 0.045). Candidate proteins were mainly involved in antigen processing and presentation, stem cell differentiation, and type I interferon pathways.
SUPPLEMENTARY INFORMATION
The online version contains supplementary material available at 10.1007/s43657-022-00070-1.
未标记
由于前列腺癌（PCa）是全球最常被诊断出的癌症之一，识别潜在的预后生物标志物至关重要。在本研究中，从癌症蛋白质组图谱（TCPA）和癌症基因组图谱（TCGA）收集了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。基于每个患者的风险评分，使用机器学习算法构建了综合预后相关蛋白（IPRPs）模型。IPRPs模型表明，高表达（=0.016）和低表达（=0.017）与PCa患者的不良预后显著相关。免疫组织化学（IHC）染色和蛋白质印迹（WB）分析显示，在验证队列中，肿瘤组织和正常组织之间的和蛋白存在显著差异表达。根据整体IHC评分，低表达（<0.0001）和高表达（=0.0001）的患者与不良预后显著相关。此外，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，低表达组与高表达组相比，（<0.05）、（<0.001）和（<0.05）水平显著升高。低表达患者的记忆B细胞（=0.002）、CD8+T细胞（<0.001）、调节性T细胞（=0.006）、M2型巨噬细胞（<0.001）浸润显著更高，而幼稚B细胞（=0.002）、浆细胞（<0.001）、静息记忆CD4+T细胞（<0.001）和嗜酸性粒细胞（=0.045）浸润显著更低。候选蛋白主要参与抗原加工和呈递、干细胞分化和I型干扰素途径。
补充信息
在线版本包含可在10.1007/s43657-022-00070-1获取的补充材料。
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