Department of Urology, The Affiliated Sir Run Run Hospital of Nanjing Medical University, Nanjing 211100, Jiangsu Province, China.
Department of Gastrointestinal Surgery, Nanjing Jiangning Hospital, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 211100, Jiangsu, China.
Int Immunopharmacol. 2021 Jan;90:107119. doi: 10.1016/j.intimp.2020.107119. Epub 2020 Nov 24.
Immune cell infiltration into tumor tissue is closely related to the clinical outcomes of patients with clear cell renal cell carcinoma (ccRCC). This study aimed to screen out potential immune genes associated with ccRCC, analyze their relationships with clinical outcomes, and construct a signature to predict ccRCC.
The transcriptome RNA-sequencing data in 539 ccRCC and 72 adjacent normal tissues were obtained from TCGA database. Biomedical computational algorithms were conducted to identify immune-related differential expressed genes (IRDGs) and enriched pathways. Then, LASSO Cox and multivariate Cox analyses were performed to screen out genes that were then used to construct the prognostic model.
A total of 116 down-regulated and 565 up-regulated IRDGs were identified. Pathway enrichment analysis suggested that IRDGs was mainly enriched in the pathway of "cytokines and cytokine receptors". The entire data of ccRCC were randomly divided into the training set and the test set with a ratio of 1:1. A 4-gene signature was then constructed using LASSO Cox analysis and multivariate Cox analysis in the training set. This prognostic signature could stratify patients into high- and low-risk groups successfully, and serve as an independent predictor when adjusted with clinical factors by univariate and multivariate Cox regression analysis. These results were verified in the test set and the entire set. Besides, the abundance of CD4 + T cells and dendritic cells increased in the high-risk group. Finally, we built a nomogram incorporating risk score and clinical factors to predict the overall survival of ccRCC patients.
These findings may contribute to the research of ccRCC in immunization part.
免疫细胞浸润肿瘤组织与透明细胞肾细胞癌(ccRCC)患者的临床结局密切相关。本研究旨在筛选与 ccRCC 相关的潜在免疫基因,分析它们与临床结局的关系,并构建一个预测 ccRCC 的特征签名。
从 TCGA 数据库中获取了 539 例 ccRCC 和 72 例相邻正常组织的转录组 RNA-seq 数据。通过生物医学计算算法识别免疫相关差异表达基因(IRDG)和富集途径。然后,进行 LASSO Cox 和多变量 Cox 分析以筛选出基因,然后用于构建预后模型。
共鉴定出 116 个下调和 565 个上调的 IRDG。通路富集分析表明,IRDG 主要富集在“细胞因子和细胞因子受体”通路中。整个 ccRCC 数据随机分为训练集和测试集,比例为 1:1。然后使用 LASSO Cox 分析和多变量 Cox 分析在训练集中构建了一个 4 基因特征签名。该预后特征签名可以成功地将患者分为高风险和低风险组,并通过单变量和多变量 Cox 回归分析在调整临床因素后作为独立预测因子。这些结果在测试集和整个数据集上得到了验证。此外,高风险组中 CD4+T 细胞和树突状细胞的丰度增加。最后,我们构建了一个包含风险评分和临床因素的列线图,以预测 ccRCC 患者的总生存率。
这些发现可能有助于 ccRCC 免疫部分的研究。