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一种用于预测分化型甲状腺癌预后的七基因自噬相关特征。

A seven-autophagy-related gene signature for predicting the prognosis of differentiated thyroid carcinoma.

作者信息

Li Chengxin, Yuan Qianqian, Xu Gaoran, Yang Qian, Hou Jinxuan, Zheng Lewei, Wu Gaosong

机构信息

Department of Breast & Thyroid Surgery, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China.

出版信息

World J Surg Oncol. 2022 Apr 23;20(1):129. doi: 10.1186/s12957-022-02590-6.

Abstract

BACKGROUND

Numerous studies have implicated autophagy in the pathogenesis of thyroid carcinoma. This investigation aimed to establish an autophagy-related gene model and nomogram that can help predict the overall survival (OS) of patients with differentiated thyroid carcinoma (DTHCA).

METHODS

Clinical characteristics and RNA-seq expression data from TCGA (The Cancer Genome Atlas) were used in the study. We also downloaded autophagy-related genes (ARGs) from the Gene Set Enrichment Analysis website and the Human Autophagy Database. First, we assigned patients into training and testing groups. R software was applied to identify differentially expressed ARGs for further construction of a protein-protein interaction (PPI) network for gene functional analyses. A risk score-based prognostic risk model was subsequently developed using univariate Cox regression and LASSO-penalized Cox regression analyses. The model's performance was verified using Kaplan-Meier (KM) survival analysis and ROC curve. Finally, a nomogram was constructed for clinical application in evaluating the patients with DTHCA. Finally, a 7-gene prognostic risk model was developed based on gene set enrichment analysis.

RESULTS

Overall, we identified 54 differentially expressed ARGs in patients with DTHCA. A new gene risk model based on 7-ARGs (CDKN2A, FGF7, CTSB, HAP1, DAPK2, DNAJB1, and ITPR1) was developed in the training group and validated in the testing group. The predictive accuracy of the model was reflected by the area under the ROC curve (AUC) values. Univariate and multivariate Cox regression analysis indicated that the model could independently predict the prognosis of patients with THCA. The constrained nomogram derived from the risk score and age also showed high prediction accuracy.

CONCLUSIONS

Here, we developed a 7-ARG prognostic risk model and nomogram for differentiated thyroid carcinoma patients that can guide clinical decisions and individualized therapy.

摘要

背景

大量研究表明自噬与甲状腺癌的发病机制有关。本研究旨在建立一个自噬相关基因模型和列线图,以帮助预测分化型甲状腺癌(DTHCA)患者的总生存期(OS)。

方法

本研究使用了来自TCGA(癌症基因组图谱)的临床特征和RNA测序表达数据。我们还从基因集富集分析网站和人类自噬数据库下载了自噬相关基因(ARG)。首先,我们将患者分为训练组和测试组。应用R软件识别差异表达的ARG,以进一步构建蛋白质-蛋白质相互作用(PPI)网络进行基因功能分析。随后,使用单变量Cox回归和LASSO惩罚Cox回归分析开发了基于风险评分的预后风险模型。使用Kaplan-Meier(KM)生存分析和ROC曲线验证了该模型的性能。最后,构建了一个列线图用于DTHCA患者的临床评估。最后,基于基因集富集分析开发了一个7基因预后风险模型。

结果

总体而言,我们在DTHCA患者中鉴定出54个差异表达的ARG。在训练组中开发了一个基于7个ARG(CDKN2A、FGF7、CTSB、HAP1、DAPK2、DNAJB1和ITPR1)的新基因风险模型,并在测试组中进行了验证。该模型的预测准确性通过ROC曲线下面积(AUC)值来反映。单变量和多变量Cox回归分析表明,该模型可以独立预测THCA患者的预后。由风险评分和年龄得出的受限列线图也显示出较高的预测准确性。

结论

在此,我们为分化型甲状腺癌患者开发了一个7-ARG预后风险模型和列线图,可指导临床决策和个体化治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4d9b/9034603/6f8c5675507d/12957_2022_2590_Fig1_HTML.jpg

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