Wu Zhenyu, Wu Zhenquan, Zeng Jie, Liu Yaxuan, Wang Yue, Li Huixin, Xia Taolin, Liu Weitao, Lin Zhe, Xu Wenfeng
Department of Urology, The First People’s Hospital of Foshan, Foshan, P.R. China.
Department of Thoracic Surgery, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, P.R. China.
Aging (Albany NY). 2024 Jan 10;16(1):43-65. doi: 10.18632/aging.205280.
Prostate cancer (PRAD) is one of the common malignant tumors of the urinary system. In order to predict the treatment results for PRAD patients, this study proposes to develop a risk profile based on endoplasmic reticulum stress (ERS). Based on the Memorial Sloan-Kettering Cancer Center (MSKCC) cohort and the Gene Expression Omnibus database (GSE70769), we verified the predictive signature. Using a random survival forest analysis, prognostically significant ERS-related genes were found. An ERS-related risk score (ERscore) was created using multivariable Cox analysis. In addition, the biological functions, genetic mutations and immune landscape related to ERscore are also studied to reveal the underlying mechanisms related to ERS in PRAD. We further explored the ERscore-related mechanisms by profiling a single-cell RNA sequencing (scRNA-seq) dataset (GSE137829) and explored the oncogenic role of ASNS in PRAD through experiments. The risk signature composed of eight ERS-related genes constructed in this study is an independent prognostic factor and validated in the MSKCC and GSE70769 data sets. The scRNA-seq data additionally revealed that several carcinogenic pathways were noticeably overactivated in the group with high ERS scores. As one of the prognostic genes, ASNS will significantly inhibit the proliferation, migration and invasion abilities of PRAD cells after its expression is interfered with. In conclusion, this study developed a novel risk-specific ERS-based clinical treatment strategy for patients with PRAD.
前列腺癌（PRAD）是泌尿系统常见的恶性肿瘤之一。为了预测PRAD患者的治疗结果，本研究提出基于内质网应激（ERS）制定风险模型。基于纪念斯隆凯特琳癌症中心（MSKCC）队列和基因表达综合数据库（GSE70769），我们验证了预测特征。通过随机生存森林分析，发现了具有预后意义的ERS相关基因。使用多变量Cox分析创建了一个与ERS相关的风险评分（ERscore）。此外，还研究了与ERscore相关的生物学功能、基因突变和免疫格局，以揭示PRAD中与ERS相关的潜在机制。我们通过分析单细胞RNA测序（scRNA-seq）数据集（GSE137829）进一步探索了与ERscore相关的机制，并通过实验探索了ASNS在PRAD中的致癌作用。本研究构建的由8个与ERS相关基因组成的风险特征是一个独立的预后因素，并在MSKCC和GSE70769数据集中得到验证。scRNA-seq数据还显示，在ERS评分高的组中，几种致癌途径明显过度激活。作为预后基因之一，ASNS表达受到干扰后将显著抑制PRAD细胞的增殖、迁移和侵袭能力。总之，本研究为PRAD患者制定了一种基于ERS的新型风险特异性临床治疗策略。
