Department of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Department of Pathology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
Front Endocrinol (Lausanne). 2023 Mar 10;14:1090277. doi: 10.3389/fendo.2023.1090277. eCollection 2023.
Endoplasmic reticulum stress (ERS) has sizeable affect on cancer proliferation, metastasis, immunotherapy and chemoradiotherapy resistance. However, the effect of ERS on the biochemical recurrence (BCR) of prostate cancer patients remains elusive. Here, we generated an ERS-related genes risk signature to evaluate the physiological function of ERS in PCa with BCR.
We collected the ERS-related genes from the GeneCards. The edgeR package was used to screen the differential ERS-related genes in PCa from TCGA datasets. ERS-related gene risk signature was then established using LASSO and multivariate Cox regression models and validated by GEO data sets. Nomogram was developed to assess BCR-free survival possibility. Meanwhile, the correlations between ERS-related signature, gene mutations, drug sensitivity and tumor microenvironment were also investigated.
We obtained an ERS risk signature consisting of five genes (AFP, COL10A1, DNAJB1, EGF and PTGS2). Kaplan Meier survival analysis and ROC Curve analysis indicated that the high risk score of ERS-related gene signature was associated with poor BCR-free prognosis in PCa patients. Besides, immune cell infiltration and immune checkpoint expression levels differed between high- and low-risk scoring subgroups. Moreover, drug sensitivity analyzed indicated that high-risk score group may be involved in apoptosis pathway.
This study comprehensively analyzed the characteristics of ERS related genes in PCa, and created a five-gene signature, which could effectively predict the BCR time of PCa patients. Targeting ERS related genes and pathways may provide potential guidance for the treatment of PCa.
内质网应激（ERS）对癌症增殖、转移、免疫治疗和放化疗耐药有很大影响。然而，ERS 对前列腺癌患者生化复发（BCR）的影响仍不清楚。在这里，我们生成了一个与 ERS 相关的基因风险特征，以评估 ERS 在具有 BCR 的前列腺癌中的生理功能。
我们从 GeneCards 中收集了与 ERS 相关的基因。使用 edgeR 包筛选 TCGA 数据集前列腺癌中差异表达的 ERS 相关基因。然后使用 LASSO 和多变量 Cox 回归模型建立 ERS 相关基因风险特征，并通过 GEO 数据集进行验证。开发了列线图来评估 BCR 无复发生存的可能性。同时，还研究了 ERS 相关特征与基因突变、药物敏感性和肿瘤微环境之间的相关性。
我们获得了一个由五个基因（AFP、COL10A1、DNAJB1、EGF 和 PTGS2）组成的 ERS 风险特征。Kaplan-Meier 生存分析和 ROC 曲线分析表明，ERS 相关基因特征的高风险评分与前列腺癌患者的不良 BCR 无复发生存相关。此外，高风险评分亚组和低风险评分亚组之间的免疫细胞浸润和免疫检查点表达水平存在差异。此外，药物敏感性分析表明，高风险评分组可能参与了细胞凋亡途径。
本研究全面分析了前列腺癌中 ERS 相关基因的特征，并构建了一个由五个基因组成的特征，可有效预测前列腺癌患者的 BCR 时间。靶向 ERS 相关基因和途径可能为前列腺癌的治疗提供潜在的指导。
