Liu Huan Rui, Peng Xiang, Li Sen Lin, Gou Xin
Department of Urology, The First Hospital of Chongqing Medical University, Chongqing 400016, China.
Chongqing Key Laboratory of Molecular Tumor and Epigenetics, Chongqing 400016, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2023 Oct 18;55(5):793-801. doi: 10.19723/j.issn.1671-167X.2023.05.004.
To investigate the correlation between the human epidermal growth factor receptor-2-related genes (HRGs) and survival prognosis of bladder cancer and to construct a predictive model for survival prognosis of bladder cancer patients based on HRGs.
HRGs in bladder cancer were found by downloading bladder tumor tissue mRNA sequencing data and clinical data from the cancer genome atlas (TCGA), downloading HER-2 related genes from the molecular signatures database (MsigDB), and crossing the two databases. Further identifying HRGs associated with bladder cancer survival ( < 0.05) by using single and multi-factor Cox regression analysis and constructing HRGs risk score model (HRSM), the bladder cancer patients were categorized into high-risk and low-risk groups accor-ding to the median risk score. Survival analysis of the patients in high- and low-risk groups was conducted using R language and correlation of HRGs with clinical characteristics. A multi-factor Cox regression analysis was used to verify the independent factors affecting the prognosis of the patients with bladder cancer. The area under the curve (AUC) of the receiver operating characteristic curve (ROC) of HRSM was calculated, and a nomogram was constructed for survival prediction of the bladder cancer patients. Analysis of HRSM and patient immune cell infiltration correlation was made using the TIMER database.
A total of 13 HRGs associated with patient survival were identified in this study. Five genes (, , , and ) were selected for HRSM by multi-factor Cox regression analysis. The 5-year survival rate of the bladder cancer patients in the high-risk group was significantly lower than that of the patients in the low-risk group. High expression of was found to be significantly and negatively correlated with tumor grade and stage by clinical correlation analysis, while was found to be the opposite; Increased expression of was associated with high grade, however, the high expression ofshowed the opposite result. And no significant correlation was found between expression and clinical features. Correlation analysis of HRSM with immune cells revealed a positive correlation between risk score and infiltration of dendritic cells, CD8T cells, CD4T cells, neutrophils and macrophages.
HRGs have an important role in the prognosis of bladder cancer patients and may serve as new predictive biomarkers and potential targets for treatment.
探讨人表皮生长因子受体2相关基因(HRGs)与膀胱癌生存预后的相关性,并基于HRGs构建膀胱癌患者生存预后预测模型。
通过从癌症基因组图谱(TCGA)下载膀胱肿瘤组织mRNA测序数据和临床数据,从分子特征数据库(MsigDB)下载HER-2相关基因,并对两个数据库进行交叉,找出膀胱癌中的HRGs。通过单因素和多因素Cox回归分析进一步鉴定与膀胱癌生存相关的HRGs(P<0.05),构建HRGs风险评分模型(HRSM),根据中位风险评分将膀胱癌患者分为高风险组和低风险组。使用R语言对高、低风险组患者进行生存分析以及HRGs与临床特征的相关性分析。采用多因素Cox回归分析验证影响膀胱癌患者预后的独立因素。计算HRSM的受试者工作特征曲线(ROC)的曲线下面积(AUC),并构建列线图用于膀胱癌患者的生存预测。使用TIMER数据库分析HRSM与患者免疫细胞浸润的相关性。
本研究共鉴定出13个与患者生存相关的HRGs。通过多因素Cox回归分析选择了5个基因(、、、和)用于构建HRSM。高风险组膀胱癌患者的5年生存率显著低于低风险组患者。临床相关性分析发现,的高表达与肿瘤分级和分期呈显著负相关,而的情况则相反;的表达增加与高级别相关,然而,的高表达结果相反。且的表达与临床特征之间未发现显著相关性。HRSM与免疫细胞的相关性分析显示,风险评分与树突状细胞、CD8 T细胞、CD4 T细胞、中性粒细胞和巨噬细胞的浸润呈正相关。
HRGs在膀胱癌患者的预后中具有重要作用,可能作为新的预测生物标志物和潜在治疗靶点。