一种新的铁死亡相关长链非编码RNA风险模型预测甲状腺乳头状癌患者的预后

A New Ferroptosis-Related Long Non-Coding RNA Risk Model Predicts the Prognosis of Patients With Papillary Thyroid Cancer.

作者信息

Zhao Jun Yu, Yao Jin Ming, Zhang Xin Zhong, Wang Kai Li, Jiang Shan, Guo Si Yi, Sheng Qi Qi, Liao Lin, Dong Jian Jun

机构信息

Department of Endocrinology and Metabology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Institute of Nephrology, Ji'nan 250014, China.

Department of Endocrinology and Metabology, Shandong Provincial Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Ji'nan 250014, China.

出版信息

World J Oncol. 2024 Aug;15(4):648-661. doi: 10.14740/wjon1838. Epub 2024 Jul 5.

DOI:10.14740/wjon1838

PMID:38993258

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11236373/

Abstract

BACKGROUND

Ferroptosis is a novel form of regulated cell death that involves in cancer progression. However, the role of ferroptosis-related long non-coding RNAs (lncRNAs) in papillary thyroid cancer (PTC) remains to be elucidated. The purpose of this paper was to clarify the prognostic value of ferroptosis-related lncRNAs in PTC.

METHODS

The transcriptome data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. The correlation between ferroptosis-related genes (FRGs) and lncRNA was determined using Pearson correlation analysis. Multivariate Cox regression model (P < 0.01) was performed to establish a ferroptosis-related lncRNAs risk model. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, risk curve and nomograms were then performed to assess the accuracy and clinical applicability of prognostic models. The correlations between the prognosis model and clinicopathological variables, immune and m6A were analyzed. Finally, assays were performed to verify the role of LINC00900, LINC01614 and PARAL1 on the proliferation, migration and invasion in TPC-1 and BCPAP cells, as well as the relationship between three lncRNAs and ferroptosis.

RESULTS

A five-ferroptosis-related lncRNAs (PARAL1, LINC00900, DPH6-DT, LINC01614, LPP-AS2) risk model was constructed. Based on the risk score, samples were divided into the high- and low-risk groups. Patients in the low-risk group had better prognosis than those in high-risk group. Compared to traditional clinicopathological features, risk score was more accurate in predicting prognosis in patients with PTC. Additionally, the difference of immune cell, function and checkpoints was observed between two groups. Moreover, experiments showed that LINC00900 promoted the proliferation, migration and invasion in TPC-1 and BCPAP cells, while LINC01614 and PARAL1 revealed opposite effects, all of which were related to ferroptosis.

CONCLUSIONS

In summary, we identified a five-ferroptosis-related lncRNAs risk model to predict the prognosis of PTC. Furthermore, our study also revealed that LINC00900 functioned as a tumor suppressor lncRNA, LINC01614 and PARAL1 as an oncogenic lncRNA in PTC.

摘要

背景

铁死亡是一种新型的程序性细胞死亡形式，与癌症进展有关。然而，铁死亡相关长链非编码RNA（lncRNA）在甲状腺乳头状癌（PTC）中的作用仍有待阐明。本文旨在明确铁死亡相关lncRNA在PTC中的预后价值。

方法

从癌症基因组图谱（TCGA）数据库下载转录组数据和临床信息。使用Pearson相关分析确定铁死亡相关基因（FRG）与lncRNA之间的相关性。采用多变量Cox回归模型（P<0.01）建立铁死亡相关lncRNA风险模型。然后进行Kaplan-Meier生存分析、受试者工作特征（ROC）曲线、风险曲线和列线图，以评估预后模型的准确性和临床适用性。分析预后模型与临床病理变量、免疫和m6A之间的相关性。最后，进行实验以验证LINC00900、LINC01614和PARAL1对TPC-1和BCPAP细胞增殖、迁移和侵袭的作用，以及三种lncRNA与铁死亡之间的关系。

结果

构建了一个包含五个铁死亡相关lncRNA（PARAL1、LINC00900、DPH6-DT、LINC01614、LPP-AS2）的风险模型。根据风险评分，将样本分为高风险组和低风险组。低风险组患者的预后优于高风险组。与传统临床病理特征相比，风险评分在预测PTC患者预后方面更准确。此外，观察到两组之间免疫细胞、功能和检查点的差异。而且，实验表明LINC00900促进TPC-1和BCPAP细胞的增殖、迁移和侵袭，而LINC01614和PARAL1则显示出相反的作用，所有这些都与铁死亡有关。