Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei, China.
Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030 Hubei, China.
Oxid Med Cell Longev. 2021 Nov 11;2021:4548594. doi: 10.1155/2021/4548594. eCollection 2021.
Redox homeostasis is the key to cell survival, and its imbalance can promote the occurrence and progression of tumors. However, it remains unclear whether these redox-related genes (RRGs) have potential roles in the tumor microenvironment, immunotherapy, and drug sensitivity. Here, we performed a systematic and comprehensive analysis of 489 prostate cancer (PC) samples from The Cancer Genome Atlas database and 214 PC samples from 8 datasets in the Gene Expression Omnibus database to determine redox modification patterns and the redox scoring system for PC. We identified two modification patterns (Redox_A and Redox_B) in PC using unsupervised consensus clustering based on 1410 differential expression RRGs. We then compared the prognostic value, tumor microenvironment characteristics, immune cell infiltration, and molecular characteristics of the two patterns. The Redox_A pattern was significantly enriched in the carcinogenic activation signaling pathways and had a poor prognosis, while the Redox_B pattern was mainly enriched in a variety of metabolic and redox pathways and had a good prognosis. Next, redox-related characteristic genes were extracted from these two patterns, and a scoring system (Redox_score) was constructed to evaluate PC patients. Further analysis indicated that lower Redox_score patients had a better prognosis, while higher Redox_score patients had a higher tumor mutation burden, driver gene mutation rate, and immune checkpoint inhibitor gene expression. We also found that higher Redox_score patients were more responsive to anti-PD-1 immunotherapy. Moreover, Redox_score was determined to be significantly correlated with anticancer drug sensitivity and resistance. Our study provides a comprehensive analysis of redox modifications in PC and reveals new patterns of PC based on RRGs, which will provide insights into the complex mechanisms of PC and develop more effective individualized therapeutic strategies.
氧化还原平衡是细胞存活的关键,其失衡可促进肿瘤的发生和发展。然而,目前尚不清楚这些氧化还原相关基因(RRGs)在肿瘤微环境、免疫治疗和药物敏感性方面是否具有潜在作用。在这里,我们对来自癌症基因组图谱数据库的 489 个前列腺癌(PC)样本和来自基因表达综合数据库的 8 个数据集的 214 个 PC 样本进行了系统和全面的分析,以确定氧化还原修饰模式和 PC 的氧化还原评分系统。我们使用基于 1410 个差异表达 RRGs 的无监督共识聚类对 PC 进行了分析,确定了两种修饰模式(Redox_A 和 Redox_B)。然后,我们比较了这两种模式的预后价值、肿瘤微环境特征、免疫细胞浸润和分子特征。Redox_A 模式在致癌激活信号通路中显著富集,预后较差,而 Redox_B 模式主要富集在各种代谢和氧化还原通路中,预后较好。接下来,从这两种模式中提取氧化还原相关特征基因,并构建评分系统(Redox_score)来评估 PC 患者。进一步分析表明,Redox_score 较低的患者预后较好,而 Redox_score 较高的患者肿瘤突变负担、驱动基因突变率和免疫检查点抑制剂基因表达水平较高。我们还发现,Redox_score 较高的患者对抗 PD-1 免疫治疗的反应更好。此外,Redox_score 与抗癌药物敏感性和耐药性显著相关。我们的研究全面分析了 PC 中的氧化还原修饰,并基于 RRGs 揭示了 PC 的新模式,这将为深入了解 PC 的复杂机制并开发更有效的个体化治疗策略提供新的思路。