Wu Xin, Li Fenghua, Xie Wenjie, Gong Binbin, Fu Bin, Chen Weimin, Zhou Libo, Luo Lianmin
Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Front Oncol. 2023 Aug 3;13:1184841. doi: 10.3389/fonc.2023.1184841. eCollection 2023.
Oxidative stress plays a significant role in the tumorigenesis and progression of tumors. We aimed to develop a prognostic signature using oxidative stress-related genes (ORGs) to predict clinical outcome and provide light on the immunotherapy responses of clear cell renal cell carcinoma (ccRCC).
The information of ccRCC patients were collected from the TCGA and the E-MTAB-1980 datasets. Univariate Cox regression analysis and least absolute shrinkage and selection operator (LASSO) were conducted to screen out overall survival (OS)-related genes. Then, an ORGs risk signature was built by multivariate Cox regression analyses. The performance of the risk signature was evaluated with Kaplan-Meier (K-M) survival. The ssGSEA and CIBERSORT algorithms were performed to evaluate immune infiltration status. Finally, immunotherapy responses was analyzed based on expression of several immune checkpoints.
A prognostic 9-gene signature with , , , , , , , , and . The patients in the high risk group had apparently poor survival (TCGA: < 0.001; E-MTAB-1980: < 0.001). The AUC of the signature was 0.81 at 1 year, 0.76 at 3 years, and 0.78 at 5 years in the TCGA, respectively, and was 0.8 at 1 year, 0.82 at 3 years, and 0.83 at 5 years in the E-MTAB-1980, respectively. Independent prognostic analysis proved the stable clinical prognostic value of the signature (TCGA cohort: HR = 1.188, 95% CI =1.142-1.236, < 0.001; E-MTAB-1980 cohort: HR =1.877, 95% CI= 1.377-2.588, < 0.001). Clinical features correlation analysis proved that patients in the high risk group were more likely to have a larger range of clinical tumor progression. The ssGSEA and CIBERSORT analysis indicated that immune infiltration status were significantly different between two risk groups. Finally, we found that patients in the high risk group tended to respond more actively to immunotherapy.
We developed a robust prognostic signature based on ORGs, which may contribute to predict survival and guide personalize immunotherapy of individuals with ccRCC.
氧化应激在肿瘤的发生和发展中起重要作用。我们旨在利用氧化应激相关基因（ORGs）开发一种预后特征，以预测临床结果，并为透明细胞肾细胞癌（ccRCC）的免疫治疗反应提供线索。
从TCGA和E-MTAB-1980数据集中收集ccRCC患者的信息。进行单变量Cox回归分析和最小绝对收缩和选择算子（LASSO）以筛选出与总生存期（OS）相关的基因。然后，通过多变量Cox回归分析建立ORGs风险特征。用Kaplan-Meier（K-M）生存法评估风险特征的性能。采用ssGSEA和CIBERSORT算法评估免疫浸润状态。最后，基于几种免疫检查点的表达分析免疫治疗反应。
一个具有 、 、 、 、 、 、 、 和 的预后9基因特征。高危组患者的生存期明显较差（TCGA：<0.001；E-MTAB-1980：<0.001）。在TCGA中，该特征在1年时的AUC为0.81，3年时为0.76，5年时为0.78；在E-MTAB-1980中，1年时为0.8，3年时为0.82，5年时为0.83。独立预后分析证明了该特征具有稳定的临床预后价值（TCGA队列：HR = 1.188，95%CI = 1.142 - 1.236，<0.001；E-MTAB-1980队列：HR = 1.877，95%CI = 1.377 - 2.588，<0.001）。临床特征相关性分析证明，高危组患者的临床肿瘤进展范围更大。ssGSEA和CIBERSORT分析表明，两个风险组之间的免疫浸润状态存在显著差异。最后，我们发现高危组患者对免疫治疗的反应往往更积极。
我们基于ORGs开发了一种可靠的预后特征，这可能有助于预测ccRCC患者的生存期并指导个性化免疫治疗。
