Department of Urology, The Affiliated Lihuili Hospital, Ningbo University, Ningbo, China.
Department of Urology, Ningbo Medical Centre Lihuili Hospital, Ningbo, China.
J Clin Lab Anal. 2022 Jun;36(6):e24409. doi: 10.1002/jcla.24409. Epub 2022 Apr 20.
Clear cell renal cell carcinoma (ccRCC) is the most common malignant tumor of the kidney and is characterized by poor prognosis. We sought to build an immune-related prognostic signature and investigate its relationship with immunotherapy response in ccRCC.
Immune-related genes were identified by ssGSEA and WGCNA. The prognostic signature was conducted via univariate, least absolute shrinkage and selection operator, and multivariable Cox regression analyses. Kaplan-Meier analysis, PCA, t-SNE, and ROC were used to evaluate the risk model.
A total of 119 immune-related genes associated with prognosis were screened out. Six immune-related genes (CSF1, CD5L, AIM2, TIMP3, IRF6, and HHLA2) were applied to construct a prognostic signature for KIRC. Kaplan-Meier analysis showed that patients in high-risk group had a poorer survival outcome than in low-risk group. The 1-, 3- and 5-year AUC of the prognostic signature was 0.754, 0.715, and 0.739, respectively. Univariate and multivariate Cox regression models demonstrated that the risk signature was an independent prognostic factor for KIRC survival. GSEA analysis suggested that the high-risk group was concentrated on immune-related pathways. The high-risk group with more regulatory T-cell infiltration showed a higher expression of immune negative regulation genes. The risk score had positively relationship with TIDE score and negatively with the response of immunotherapy. The IC50 values of axitinib, sunitinib, sorafenib, and temsirolimus were lower in the high-risk group.
Our study defined a robust signature that may be promising for predicting clinical outcomes and immunotherapy and targeted therapy response in ccRCC patients.
透明细胞肾细胞癌（ccRCC）是最常见的肾恶性肿瘤，其预后较差。我们试图构建一个免疫相关的预后特征，并研究其与 ccRCC 免疫治疗反应的关系。
通过 ssGSEA 和 WGCNA 鉴定免疫相关基因。通过单变量、最小绝对收缩和选择算子以及多变量 Cox 回归分析构建预后特征。Kaplan-Meier 分析、PCA、t-SNE 和 ROC 用于评估风险模型。
筛选出 119 个与预后相关的免疫相关基因。应用 6 个免疫相关基因（CSF1、CD5L、AIM2、TIMP3、IRF6 和 HHLA2）构建 KIRC 的预后特征。Kaplan-Meier 分析表明，高风险组患者的生存结局较 低风险组差。预后特征的 1 年、3 年和 5 年 AUC 分别为 0.754、0.715 和 0.739。单变量和多变量 Cox 回归模型表明，风险特征是 KIRC 生存的独立预后因素。GSEA 分析表明，高风险组集中在免疫相关途径。调节性 T 细胞浸润较多的高风险组表现出更高的免疫负调节基因表达。风险评分与 TIDE 评分呈正相关，与免疫治疗反应呈负相关。高风险组中阿昔替尼、舒尼替尼、索拉非尼和替西罗莫司的 IC50 值较低。
本研究定义了一个稳健的特征，可能有望预测 ccRCC 患者的临床结局和免疫治疗及靶向治疗反应。
