Wang Shuo, Yu Ziyi, Cao Yudong, Du Peng, Ma Jinchao, Ji Yongpeng, Yang Xiao, Zhao Qiang, Hong Baoan, Yang Yong, Hai Yanru, Li Junhui, Mao Yufeng, Wu Shuangxiu
Urological Department, Peking University Cancer Hospital & Institute, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Beijing, China.
Genetron Health (Beijing) Technology, Co. Ltd, Beijing, China.
Cancer Control. 2024 Jan-Dec;31:10732748241272713. doi: 10.1177/10732748241272713.
Accurate survival predictions and early interventional therapy are crucial for people with clear cell renal cell carcinoma (ccRCC).
In this retrospective study, we identified differentially expressed immune-related (DE-IRGs) and oncogenic (DE-OGs) genes from The Cancer Genome Atlas (TCGA) dataset to construct a prognostic risk model using univariate Cox regression and least absolute shrinkage and selection operator (LASSO) analysis. We compared the immunogenomic characterization between the high- and low-risk patients in the TCGA and the PUCH cohort, including the immune cell infiltration level, immune score, immune checkpoint, and T-effector cell- and interferon (IFN)-γ-related gene expression.
A prognostic risk model was constructed based on 9 DE-IRGs and 3 DE-OGs and validated in the training and testing TCGA datasets. The high-risk group exhibited significantly poor overall survival compared with the low-risk group in the training ( < 0.0001), testing ( = 0.016), and total ( < 0.0001) datasets. The prognostic risk model provided accurate predictive value for ccRCC prognosis in all datasets. Decision curve analysis revealed that the nomogram showed the best net benefit for the 1-, 3-, and 5-year risk predictions. Immunogenomic analyses of the TCGA and PUCH cohorts showed higher immune cell infiltration levels, immune scores, immune checkpoint, and T-effector cell- and IFN-γ-related cytotoxic gene expression in the high-risk group than in the low-risk group.
The 12-gene prognostic risk model can reliably predict overall survival outcomes and is strongly associated with the tumor immune microenvironment of ccRCC.
准确的生存预测和早期介入治疗对于肾透明细胞癌(ccRCC)患者至关重要。
在这项回顾性研究中,我们从癌症基因组图谱(TCGA)数据集中鉴定出差异表达的免疫相关(DE-IRGs)和致癌(DE-OGs)基因,使用单变量Cox回归和最小绝对收缩和选择算子(LASSO)分析构建预后风险模型。我们比较了TCGA和PUCH队列中高风险和低风险患者之间的免疫基因组特征,包括免疫细胞浸润水平、免疫评分、免疫检查点以及T效应细胞和干扰素(IFN)-γ相关基因表达。
基于9个DE-IRGs和3个DE-OGs构建了预后风险模型,并在TCGA训练集和测试集中进行了验证。在训练集(<0.0001)、测试集(=0.016)和总数据集(<0.0001)中,高风险组的总生存期明显低于低风险组。预后风险模型为所有数据集中的ccRCC预后提供了准确的预测价值。决策曲线分析显示,列线图在1年、3年和5年风险预测中显示出最佳的净效益。TCGA和PUCH队列的免疫基因组分析显示,高风险组的免疫细胞浸润水平、免疫评分、免疫检查点以及T效应细胞和IFN-γ相关细胞毒性基因表达均高于低风险组。
12基因预后风险模型能够可靠地预测总生存结果,并与ccRCC的肿瘤免疫微环境密切相关。