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构建一个与铁死亡相关的八个基因特征,用于预测甲状腺癌的预后和免疫浸润。

Construction of a ferroptosis-related eight gene signature for predicting the prognosis and immune infiltration of thyroid cancer.

机构信息

Department of Endocrinology and Metabolism, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.

Department of Cardiology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.

出版信息

Front Endocrinol (Lausanne). 2022 Nov 4;13:997873. doi: 10.3389/fendo.2022.997873. eCollection 2022.

Abstract

BACKGROUND

Thyroid cancer is the most common malignant tumor of the endocrine system. Most patients with thyroid cancer have a good prognosis, although a small proportion experience recurrence and metastasis and have a poor prognosis. Ferroptosis is a novel form of regulated cell death (RCD); previous studies have confirmed that ferroptosis was associated with thyroid cancer. The purpose of this study was to investigate the key ferroptosis-related genes in thyroid cancer and their relationship with prognosis and immune cell infiltration.

METHODS

In this study, 497 thyroid cancer RNA expression datasets were downloaded from the cancer genome atlas (TCGA) cohort and a prognostic risk model for eight ferroptosis-related genes (FRGs) was constructed by Lasso-Cox regression. The prognostic value of the risk model and the correlation of prognostic features with immune scores and tumor immune cell infiltration were systematically analyzed.

RESULTS

The prognostic risk model for eight FRGs (, , , , , , and ) were constructed and validated in training and testing cohorts. Kaplan-Meier curve and receiver operating characteristic (ROC) curve analysis confirmed that that the ferroptosis-related eight gene signature had good predictive value for the prognosis of thyroid cancer (THCA) patients. Multivariate regression analysis further showed that the risk score of the prognostic model could be used as an independent prognostic factor for THCA patients. Functional enrichment analysis showed that DEGs in high risk and low risk groups were involved in immune-related biological processes and that there were significant differences in immune cell infiltration between the two risk groups.

CONCLUSION

We identified eight key genes related to ferroptosis in THCA patients. Further studies are now needed to investigate the mechanisms involved; these genes may represent clinical diagnostic and prognostic biomarkers.

摘要

背景

甲状腺癌是内分泌系统最常见的恶性肿瘤。大多数甲状腺癌患者预后良好,尽管少数患者会复发和转移,预后较差。铁死亡是一种新型的细胞死亡形式(RCD);先前的研究证实铁死亡与甲状腺癌有关。本研究旨在探讨甲状腺癌中关键的铁死亡相关基因及其与预后和免疫细胞浸润的关系。

方法

本研究从癌症基因组图谱(TCGA)队列中下载了 497 个甲状腺癌 RNA 表达数据集,并通过 Lasso-Cox 回归构建了八个铁死亡相关基因(FRGs)的预后风险模型。系统分析了风险模型的预后价值以及预后特征与免疫评分和肿瘤免疫细胞浸润的相关性。

结果

构建并验证了八个 FRGs(,,,,,, 和 )的预后风险模型在训练和测试队列中。Kaplan-Meier 曲线和接受者操作特征(ROC)曲线分析证实,铁死亡相关的八个基因特征对甲状腺癌(THCA)患者的预后具有良好的预测价值。多变量回归分析进一步表明,预后模型的风险评分可作为 THCA 患者的独立预后因素。功能富集分析表明,高低风险组的 DEGs 参与了免疫相关的生物学过程,并且两个风险组之间的免疫细胞浸润存在显著差异。

结论

我们确定了与 THCA 患者铁死亡相关的八个关键基因。目前需要进一步研究这些基因的作用机制;这些基因可能代表临床诊断和预后的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff30/9672669/1757beae2d36/fendo-13-997873-g001.jpg

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