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基于自噬相关基因特征的儿童肾母细胞瘤总生存预后列线图

A Prognostic Nomogram for Predicting Overall Survival in Pediatric Wilms Tumor Based on an Autophagy-related Gene Signature.

机构信息

Department of Pediatrics, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.

Department of Clinical Research, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.

出版信息

Comb Chem High Throughput Screen. 2022;25(8):1385-1397. doi: 10.2174/1386207324666210826143727.

Abstract

BACKGROUND

Wilms Tumor (WT) is the most common primary renal malignancy in children. Autophagy plays dual roles in the promotion and suppression of various cancers.

OBJECTIVE

The goal of our study was to develop a novel autophagy-related gene (ARG) prognostic nomogram for WT.

METHODS

The Cancer Genome Atlas (TCGA) database was used. We screened the expression profiles of ARGs in 136 WT patients. The differentially expressed prognostic ARGs were evaluated by multivariate Cox regression analysis and survival analysis. A novel prognostic nomogram based on the ARGs and clinical characteristics was established using multivariate Cox regression analysis.

RESULTS

First, 69 differentially expressed ARGs were identified in WT patients. Then, multivariate Cox regression analysis was used to determine 4 key prognostic ARGs (CC3CL1, ERBB2, HIF-α and CXCR4) in WT. According to their ARG expression levels, the patients were clustered into high- and low-risk groups. Next, survival analysis indicated that high-risk patients had significantly poorer overall survival than low-risk patients. The results of functional enrichment analysis suggested that autophagy may play a tumor-suppressive role in the initiation of WT. Finally, a prognostic nomogram with a Harrell's concordance index (C-index) of 0.841 was used to predict the survival probability of WT patients by integrating clinical characteristics and the 4-ARG signature. The calibration curve indicated its excellent predictive performance.

CONCLUSION

In summary, the ARG signature could be a promising biomarker for monitoring the outcomes of WT. We established a novel nomogram based on the ARG signature, which accurately predicts the overall survival of WT patients.

摘要

背景

肾母细胞瘤(WT)是儿童最常见的原发性肾恶性肿瘤。自噬在促进和抑制各种癌症方面发挥着双重作用。

目的

本研究旨在构建一种新的自噬相关基因(ARG)预测肾母细胞瘤预后的列线图。

方法

利用癌症基因组图谱(TCGA)数据库,筛选 136 例 WT 患者的 ARG 表达谱。采用多变量 Cox 回归分析和生存分析评估差异表达的预后 ARG。采用多变量 Cox 回归分析建立基于 ARG 和临床特征的新型预后列线图。

结果

首先,在 WT 患者中鉴定出 69 个差异表达的 ARG。然后,采用多变量 Cox 回归分析确定 WT 中 4 个关键预后 ARG(CC3CL1、ERBB2、HIF-α和 CXCR4)。根据 ARG 的表达水平,将患者分为高风险和低风险组。接下来,生存分析表明,高危组患者的总生存明显较差。功能富集分析结果表明,自噬可能在 WT 的发生中发挥肿瘤抑制作用。最后,构建了一个预后列线图,其 Harrell 一致性指数(C 指数)为 0.841,通过整合临床特征和 4-ARG 特征,预测 WT 患者的生存概率。校准曲线表明其具有良好的预测性能。

结论

总之,ARG 特征可以作为监测 WT 患者预后的一种有前途的生物标志物。本研究建立了一种新的基于 ARG 特征的列线图,能够准确预测 WT 患者的总生存。

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