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程序性细胞死亡相关基因IL20RA促进甲状腺癌的肿瘤进展并重塑肿瘤微环境。

Programmed cell death-related gene IL20RA facilitates tumor progression and remodels tumor microenvironment in thyroid cancer.

作者信息

Wang Yuqi, Zhang Yunlong, Liu Min, Liu Yu, Zeng Yu, Zhang Wei, Wu Shuping, Hu Linfei, Ruan Xianhui, Zheng Xiangqian, Gao Ming, Zhao Jingzhu

机构信息

Department of Thyroid and Neck Tumor, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.

Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China.

出版信息

Sci Rep. 2025 Jan 28;15(1):3520. doi: 10.1038/s41598-025-87059-8.

Abstract

Programmed cell death (PCD) is a vital biological process that is essential for regulating cell progression and tumor microenvironment. This study aimed to explore the relationship between PCD-related genes expression and prognosis in thyroid cancer (THCA), especially IL20RA, as a potential prognostic marker for THCA. Data from The Cancer Genome Atlas (TCGA) database was utilized to develop a PCD-related risk prediction model based on LASSO regression along with univariate Cox regression. The correlation between PCD-related genes and immune cell infiltration was also assessed. The prognostic value of the key PCD-related gene for THCA was investigated by immunohistochemistry. The immune regulatory function and biological function of the key PCD related molecules were detected by cellular experiments. We identified four PCD-related genes (NPC2, E2F1, IL20RA, and TREM2) and constructed a risk model that exhibited excellent accuracy in predicting the prognosis of THCA. Moreover, we confirmed that high expression of IL20RA related to the poor prognosis of THCA. IL20RA promoted cell proliferation and IL20RA knockdown increased apoptosis and ferroptosis. Analysis of the immune microenvironment and detection of macrophages polarization showed that IL20RA promoted the polarization of M2 macrophages while reducing the polarization of M1. We constructed a prognostic prediction model and identified several PCD-related genes. The function of IL20RA which could potentially provide a foundation for additional investigations into diagnostic markers and treatment targets for THCA.

摘要

程序性细胞死亡(PCD)是一种重要的生物学过程,对于调节细胞进程和肿瘤微环境至关重要。本研究旨在探讨PCD相关基因表达与甲状腺癌(THCA)预后之间的关系,尤其是白细胞介素20受体A(IL20RA),作为THCA潜在的预后标志物。利用来自癌症基因组图谱(TCGA)数据库的数据,基于套索回归(LASSO)和单变量Cox回归建立了一个PCD相关风险预测模型。还评估了PCD相关基因与免疫细胞浸润之间的相关性。通过免疫组织化学研究关键PCD相关基因对THCA的预后价值。通过细胞实验检测关键PCD相关分子的免疫调节功能和生物学功能。我们鉴定出四个PCD相关基因(NPC2、E2F1、IL20RA和TREM2),并构建了一个在预测THCA预后方面具有出色准确性的风险模型。此外,我们证实IL20RA的高表达与THCA的不良预后相关。IL20RA促进细胞增殖,而敲低IL20RA可增加细胞凋亡和铁死亡。对免疫微环境的分析和巨噬细胞极化的检测表明,IL20RA促进M2巨噬细胞的极化,同时减少M1巨噬细胞的极化。我们构建了一个预后预测模型,并鉴定出几个PCD相关基因。IL20RA的功能可能为进一步研究THCA的诊断标志物和治疗靶点提供基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d527/11775127/6b8694020e74/41598_2025_87059_Fig1_HTML.jpg

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