Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Department of Thyroid and Breast Surgery, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
PeerJ. 2023 Feb 8;11:e14784. doi: 10.7717/peerj.14784. eCollection 2023.
Clear cell renal cell carcinoma (ccRCC) is considered to be related to the worse prognosis, which might in part be attributed to the early recurrence and metastasis, compared with other type of kidney cancer. Oxidative stress refers to an imbalance between production of oxidants and antioxidant defense. Accumulative studies have indicated that oxidative stress genes contribute to the tumor invasion, metastasis and drug sensitivity. However, the biological functions of oxidative stress genes in ccRCC remain largely unknown. In this study, we identified 1,399 oxidative stress genes from GeneCards with a relevance score ≥7. Data for analysis were accessed from The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) database, and were utilized as training set and validation set respectively. Univariate Cox analysis, least absolute shrinkage and selection operator (LASSO) Cox regression and multivariate Cox were employed to construct a prognostic signature in ccRCC. Finally, a prognostic signature including four different oxidative stress genes was constructed from 1,399 genes, and its predictive performance was verified through Kaplan-Meier survival analysis and the receiver operating characteristic (ROC) curve. Interestingly, we found that there was significant correlation between the expression of oxidative stress genes and the immune infiltration and the sensitivity of tumor cells to chemotherapeutics. Moreover, the highest hazard ratio gene urocortin () was chosen for further study; some necessary vitro experiments proved that the could promote the ability of ccRCC proliferation and migration and contribute to the degree of oxidative stress. In conclusion, it was promising to predict the prognosis of ccRCC through the four oxidative stress genes signature. played oncogenic roles in ccRCC by influencing proliferation and oxidative stress pathway, which was expected to be the novel therapeutic target for ccRCC.
透明细胞肾细胞癌 (ccRCC) 被认为与预后较差有关,这在一定程度上可能归因于早期复发和转移,与其他类型的肾癌相比。氧化应激是指氧化剂的产生和抗氧化防御之间的不平衡。累积的研究表明,氧化应激基因有助于肿瘤的侵袭、转移和药物敏感性。然而,氧化应激基因在 ccRCC 中的生物学功能在很大程度上仍不清楚。在这项研究中,我们从 GeneCards 中确定了 1399 个氧化应激基因,相关性评分≥7。分析数据来自癌症基因组图谱 (TCGA) 和国际癌症基因组联盟 (ICGC) 数据库,并分别用作训练集和验证集。单变量 Cox 分析、最小绝对收缩和选择算子 (LASSO) Cox 回归和多变量 Cox 用于构建 ccRCC 的预后特征。最后,从 1399 个基因中构建了一个包含四个不同氧化应激基因的预后特征,并通过 Kaplan-Meier 生存分析和接收器操作特征 (ROC) 曲线验证了其预测性能。有趣的是,我们发现氧化应激基因的表达与免疫浸润和肿瘤细胞对化疗药物的敏感性之间存在显著相关性。此外,选择最高风险比基因 urocortin () 进行进一步研究;一些必要的体外实验证明, 可以促进 ccRCC 增殖和迁移的能力,并有助于氧化应激的程度。总之,通过四个氧化应激基因特征预测 ccRCC 的预后是有希望的。 在 ccRCC 中发挥致癌作用,通过影响增殖和氧化应激途径,有望成为 ccRCC 的新治疗靶点。