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基于铜死亡相关长非编码 RNA 的膀胱癌预后风险模型的构建。

Construction of prognostic risk model of bladder cancer based on cuproptosis-related long non-coding RNAs.

机构信息

Department of Nuclear Medicine, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.

Department of Blood Transfusion, Affiliated Hospital of Jiangsu University, Zhenjiang 212001, Jiangsu Province, China.

出版信息

Zhejiang Da Xue Xue Bao Yi Xue Ban. 2023 Apr 25;52(2):139-147. doi: 10.3724/zdxbyxb-2022-0539.

Abstract

OBJECTIVES

To construct a prognosis risk model based on long noncoding RNAs (lncRNAs) related to cuproptosis and to evaluate its application in assessing prognosis risk of bladder cancer patients.

METHODS

RNA sequence data and clinical data of bladder cancer patients were downloaded from the Cancer Genome Atlas database. The correlation between lncRNAs related to cuproptosis and bladder cancer prognosis was analyzed with Pearson correlation analysis, univariate Cox regression, Lasso regression, and multivariate Cox regression. Then a cuproptosis-related lncRNA prognostic risk scoring equation was constructed. Patients were divided into high-risk and low-risk groups based on the median risk score, and the immune cell abundance between the two groups were compared. The accuracy of the risk scoring equation was evaluated using Kaplan-Meier survival curves, and the application of the risk scoring equation in predicting 1, 3 and 5-year survival rates was evaluated using receiver operating characteristic (ROC) curves. Univariate and multivariate Cox regression were used to screen for prognostic factors related to bladder cancer patients, and a prognostic risk assessment nomogram was constructed, the accuracy of which was evaluated with calibration curves.

RESULTS

A prognostic risk scoring equation for bladder cancer patients was constructed based on nine cuproptosis-related lncRNAs. Immune infiltration analysis showed that the abundances of M0 macrophages, M1 macrophages, M2 macrophages, resting mast cells and neutrophils in the high-risk group were significantly higher than those in the low-risk group, while the abundances of CD8 T cells, helper T cells, regulatory T cells and plasma cells in the low-risk group were significantly higher than those in the high-risk group (all <0.05). Kaplan-Meier survival curve analysis showed that the total survival and progression-free survival of the low-risk group were longer than those of the high-risk group (both <0.01). Univariate and multivariate Cox analysis showed that the risk score, age and tumor stage were independent factors for patient prognosis. The ROC curve analysis showed that the area under the curve (AUC) of the risk score in predicting 1, 3 and 5-year survival was 0.716, 0.697 and 0.717, respectively. When combined with age and tumor stage, the AUC for predicting 1-year prognosis increased to 0.725. The prognostic risk assessment nomogram for bladder cancer patients constructed based on patient age, tumor stage, and risk score had a prediction value that was consistent with the actual value.

CONCLUSIONS

A bladder cancer patient prognosis risk assessment model based on cuproptosis-related lncRNA has been successfully constructed in this study. The model can predict the prognosis of bladder cancer patients and their immune infiltration status, which may also provide a reference for tumor immunotherapy.

摘要

目的

构建基于与铜死亡相关的长链非编码 RNA(lncRNA)的预后风险模型,并评估其在评估膀胱癌患者预后风险中的应用。

方法

从癌症基因组图谱数据库中下载膀胱癌患者的 RNA 序列数据和临床数据。采用 Pearson 相关分析、单因素 Cox 回归、Lasso 回归和多因素 Cox 回归分析与膀胱癌预后相关的 lncRNA 与铜死亡的相关性。然后构建铜死亡相关 lncRNA 预后风险评分方程。根据中位数风险评分将患者分为高危组和低危组,并比较两组之间的免疫细胞丰度。使用 Kaplan-Meier 生存曲线评估风险评分方程的准确性,并使用受试者工作特征(ROC)曲线评估风险评分方程预测 1、3 和 5 年生存率的应用。采用单因素和多因素 Cox 回归筛选与膀胱癌患者相关的预后因素,并构建预后风险评估列线图,通过校准曲线评估其准确性。

结果

基于 9 个铜死亡相关 lncRNA 构建了膀胱癌患者的预后风险评分方程。免疫浸润分析显示,高危组 M0 巨噬细胞、M1 巨噬细胞、M2 巨噬细胞、静止肥大细胞和中性粒细胞的丰度明显高于低危组,而低危组 CD8+T 细胞、辅助性 T 细胞、调节性 T 细胞和浆细胞的丰度明显高于高危组(均<0.05)。Kaplan-Meier 生存曲线分析显示,低危组的总生存期和无进展生存期均长于高危组(均<0.01)。单因素和多因素 Cox 分析显示,风险评分、年龄和肿瘤分期是患者预后的独立因素。ROC 曲线分析显示,风险评分预测 1、3 和 5 年生存率的曲线下面积(AUC)分别为 0.716、0.697 和 0.717。当与年龄和肿瘤分期相结合时,预测 1 年预后的 AUC 增加至 0.725。基于患者年龄、肿瘤分期和风险评分构建的膀胱癌患者预后风险评估列线图具有与实际值一致的预测价值。

结论

本研究成功构建了基于铜死亡相关 lncRNA 的膀胱癌患者预后风险评估模型。该模型可预测膀胱癌患者的预后及其免疫浸润状态,也可为肿瘤免疫治疗提供参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a95/10409915/17da392d0816/ZJYB-52-02-002-g001.jpg

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