Department of Urology, Xuchang Central Hospital of Henan Province, Xuchang 461000, Henan Province, China.
Department of Urology, the Affiliated Hospital of Yangzhou University, Yangzhou 225000, Jiangsu Province, China.
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2023 Aug 25;52(4):499-509. doi: 10.3724/zdxbyxb-2023-0051.
OBJECTIVES: To construct a prediction model for the prognosis of bladder cancer patients based on the expression of ion channel-related genes (ICRGs). METHODS: ICRGs were obtained from the existing researches. The clinical information and the expression of ICRGs mRNA in breast cancer patients were obtained from the Cancer Genome Atlas database. Cox regression analysis, minimum absolute shrinkage and selection operator regression analysis were used to screen breast cancer prognosis related genes, which were verified by immunohistochemistry and qRT-PCR. The risk scoring equation for predicting the prognosis of patients with bladder cancer was constructed, and the patients were divided into high-risk group and low-risk group according to the median risk score. Immune cell infiltration was compared between the two groups. Kaplan-Meier survival curve and receiver operating characteristic (ROC) curve were used to evaluate the accuracy and clinical application value of the risk scoring equation. The factors related to the prognosis of bladder cancer patients were analyzed by univariate and multivariate Cox regression, and a nomogram for predicting the prognosis of bladder cancer patients was constructed. RESULTS: By comparing the expression levels of ICRGs in bladder cancer tissues and normal bladder tissues, 73 differentially expressed ICRGs were dentified, of which 11 were related to the prognosis of bladder cancer patients. Kaplan-Meier survival curve suggested that the risk score based on these 11 genes was negatively correlated with the prognosis of patients. The area under the ROC curve of the risk score for predicting the prognosis of patients at 1, 3 and 5 year was 0.634, 0.665 and 0.712, respectively. Stratified analysis showed that the ICRGs-based risk score performed well in predicting the prognosis of patients with American Joint Committee on Cancer (AJCC) stage Ⅲ-Ⅳ bladder cancer (<0.05), while it had a poor value in predicting the prognosis of patients with AJCC stage Ⅰ-Ⅱ (>0.05). There were significant differences in the infiltration of plasma cells, activated natural killer cells, resting mast cells and M2 macrophages between the high-risk group and the low-risk group. Cox regression analysis showed that risk score, smoking, age and AJCC stage were independently associated with the prognosis of patients with bladder cancer (<0.05). The nomogram constructed by combining risk score and clinical parameters has high accuracy in predicting the 1, 3 and 5 year overall survival rate of bladder cancer patients. CONCLUSIONS: The study shows the potential value of ICRGs in the prognostic risk assessment of bladder cancer patients. The constructed prognostic nomogram based on ICRGs risk score has high accuracy in predicting the prognosis of bladder cancer patients.
目的:基于离子通道相关基因(ICRG)的表达构建膀胱癌患者预后的预测模型。
方法:从已有的研究中获取 ICRG。从癌症基因组图谱数据库中获取乳腺癌患者的临床信息和 ICRG mRNA 的表达。使用 Cox 回归分析、最小绝对收缩和选择算子回归分析筛选与乳腺癌预后相关的基因,并通过免疫组化和 qRT-PCR 进行验证。构建预测膀胱癌患者预后的风险评分方程,并根据中位数风险评分将患者分为高风险组和低风险组。比较两组间免疫细胞浸润情况。采用 Kaplan-Meier 生存曲线和受试者工作特征(ROC)曲线评估风险评分方程的准确性和临床应用价值。采用单因素和多因素 Cox 回归分析膀胱癌患者预后的相关因素,并构建膀胱癌患者预后预测的列线图。
结果:通过比较膀胱癌组织和正常膀胱组织中 ICRG 的表达水平,鉴定出 73 个差异表达的 ICRG,其中 11 个与膀胱癌患者的预后相关。Kaplan-Meier 生存曲线提示基于这 11 个基因的风险评分与患者的预后呈负相关。预测患者 1、3 和 5 年预后的风险评分的 ROC 曲线下面积分别为 0.634、0.665 和 0.712。分层分析表明,ICRG 为基础的风险评分在预测 AJCC 分期Ⅲ-Ⅳ期膀胱癌患者的预后方面表现良好(<0.05),而在预测 AJCC 分期Ⅰ-Ⅱ期患者的预后方面价值较低(>0.05)。高风险组与低风险组间浆细胞、活化自然杀伤细胞、静止肥大细胞和 M2 巨噬细胞浸润存在显著差异。Cox 回归分析显示,风险评分、吸烟、年龄和 AJCC 分期与膀胱癌患者的预后独立相关(<0.05)。结合风险评分和临床参数构建的列线图在预测膀胱癌患者 1、3 和 5 年总生存率方面具有较高的准确性。
结论:本研究表明 ICRG 在膀胱癌患者预后风险评估中具有潜在价值。基于 ICRG 风险评分构建的预后列线图在预测膀胱癌患者预后方面具有较高的准确性。
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