广西医学

目的基于生物信息学方法探讨细胞分裂周期蛋白25B（CDC25B）基因与肾透明细胞癌（KIRC）患者预后及免疫细胞浸润的关系。方法在TCGA数据库下载33种癌症的RNAseq 数据及KIRC患者的临床病理参数数据。使用R语言软件分析CDC25B mRNA在泛癌和KIRC组织中的表达水平及其与KIRC患者临床病理参数的关系。采用Kaplan⁃Meier法分析CDC25B mRNA表达水平与KIRC患者总生存期、疾病特异性生存期及无进展间隔期的关系。绘制受试者工作特征曲线分析CDC25B mRNA表达水平在KIRC患者中的诊断效能。利用单因素及多因素COX回归模型分析CDC25B mRNA对KIRC患者预后的预测价值，构建诺莫图。采用Spearman相关性系数分析CDC25B mRNA表达水平与免疫检查点基因表达水平及免疫细胞浸润丰度的相关性。结果 CDC25B mRNA在KIRC、乳腺浸润癌、膀胱尿路上皮癌、食管癌和肝细胞癌等多种癌症中表达上调，其表达水平与KIRC患者T分期、M分期、临床分期及病理分级相关（P<0.05）。与CDC25B mRNA低表达组相比，CDC25B mRNA高表达组患者的总生存期、疾病特异性生存期及无进展间隔期较短（P<0.05）。CDC25B mRNA表达水平诊断KIRC的曲线下面积为0.759。年龄、M分期、病理分级、CDC25B mRNA表达水平与KIRC患者总生存期相关（P<0.05），基于这些参数构建的诺莫图模型对KIRC患者1年、2年、3年总生存率的预测概率与实际观测概率有较好的一致性。CDC25B mRNA与CD274、PDCD1、CTLA4、LAG3、CD276等免疫检查点基因表达水平呈正相关，与KIRC组织中活化的CD4+ T淋巴细胞、活化的CD8+ T淋巴细胞、活化的B淋巴细胞、巨噬细胞、髓源性抑制细胞和Treg细胞浸润丰度呈正相关（P<0.05）。结论 CDC25B mRNA在KIRC组织中显著上调，与患者不良预后有关，还与KIRC组织免疫细胞浸润有关，可以作为预测KIRC患者预后的独立因子。

Objective To investigate the relation between cell division cycle 25B (CDC25B) gene and prognosis and immune cell infiltration in patients with kidney renal clear cell carcinoma (KIRC) based on bioinformatics approaches. Methods RNAseq data from 33 cancer categories and clinicopathological parameter data of KIRC patients were downloaded from the TCGA database. The R language software was used to analyze CDC25B mRNA expression in pan⁃cancer and KIRC tissues, and its relation with clinicopathological parameters of KIRC patients. The Kaplan⁃Meier method was adopted to analyze the relation of CDC25B mRNA expression with overall survival, disease⁃specific survival, and progression⁃free interval of KIRC patients. The receiver operating characteristic curve was drawn to assess CDC25B mRNA expression in the diagnostic performance of KIRC patients. The univariate and multivariate COX regression model was employed to identify predictive value of CDC25B mRNA for prognosis of KIRC patients, followed by nomogram construction. The Spearman correlation coefficient was used to analyze the correlation of CDC25B mRNA expression with immune checkpoint genes expressions, and the abundance of immune cell infiltration. Results CDC25B mRNA expression was up⁃regulated in KIRC, breast invasive carcinoma, bladder urothelial carcinoma, esophageal carcinoma and liver hepatocellular carcinoma, etc., and was related to T stage, M stage, clinical stage and pathological grade of KIRC patients (P<0.05). The overall survival, disease⁃specific survival and progression⁃free interval of patients in the CDC25B mRNA high expression group were shorter than those in the CDC25B mRNA low expression group (P<0.05). Area under the curve of CDC25B mRNA expression in the diagnosis of KIRC was 0.759. Age, M stage, pathological grade and CDC25B mRNA expression were correlated with the overall survival of KIRC patients (P<0.05). The nomogram model constructed based on these parameters had favorable consistency between the predicted and actual observed probability of 1⁃, 2⁃ and 3⁃year overall survival of KIRC patients. CDC25B mRNA positively correlated with the expressions of immune checkpoint genes such as CD274, PDCD1, CTLA4, LAG3 and CD276, and positively correlated with activated CD4+ T lymphocytes, activated CD8+ T lymphocytes, activated B lymphocytes, macrophages, myeloid⁃derived suppressor cells and the abundance of Treg cells infiltration in KIRC tissues (P<0.05). Conclusion CDC25B mRNA is significantly up⁃regulated in KIRC tissues, which is related to poor prognosis of KIRC patients, and is also related to the infiltration of immune cells in KIRC tissues. It can be used as an independent factor for predicting the prognosis of KIRC patients.

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