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铁死亡相关长链非编码RNA特征预测肝细胞癌的预后和免疫微环境。

Ferroptosis-related lncRNA signature predicts the prognosis and immune microenvironment of hepatocellular carcinoma.

作者信息

Fang Chongkai, Liu Silin, Feng Kunliang, Huang Chaoyuan, Zhang Ying, Wang Jinan, Lin Hongtong, Wang Junyan, Zhong Chong

机构信息

First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, 510403, Guangdong, China.

Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510403, Guangdong, China.

出版信息

Sci Rep. 2022 Apr 22;12(1):6642. doi: 10.1038/s41598-022-10508-1.

DOI:10.1038/s41598-022-10508-1
PMID:35459272
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9033801/
Abstract

This study aimed to construct a ferroptosis-related lncRNA signature to probe the prognosis and immune infiltration of HCC patients. The Cancer Genome Atlas (TCGA) database was randomly divided into two parts, with two-thirds training and one-third testing sets. Univariate, multivariate, and least absolute selection operator (LASSO) Cox regression analyses were performed to establish a ferroptosis-related lncRNA signature. The prognostic signature was constructed by 6 ferroptosis-related lncRNAs (PCAT6, MKLN1-AS, POLH-AS1, LINC00942, AL031985.3, LINC00942) shows a promising clinical prediction value in patients with HCC. Patients with high-risk score indicated a poorer prognosis than patients with low-risk score were shown in the training set (p < 0.001) and testing set (p = 0.024). Principal component analysis (PCA) and nomogram were performed to verify the value of the prognostic signature. The area under curves (AUCs) for 1-, 3-, and 5-year survival rates were 0.784, 0.726, 0.699, respectively. Moreover, TCGA revealed that immune cell subpopulations and related functions, including cytolytic activity, MHC class I, type I and type II IFN response, were significantly different between the two risk groups. Immune checkpoints such as PDCD1, CTLA4, CD44, VTCN1 were also abnormally expressed between the two risk groups. This prognostic signature based on the ferroptosis-related lncRNAs may be promising for the clinical prediction of prognosis and immunotherapeutic responses in patients with HCC.

摘要

本研究旨在构建一种与铁死亡相关的lncRNA特征,以探究肝癌患者的预后和免疫浸润情况。癌症基因组图谱(TCGA)数据库被随机分为两部分,三分之二作为训练集,三分之一作为测试集。进行单因素、多因素和最小绝对收缩选择算子(LASSO)Cox回归分析,以建立与铁死亡相关的lncRNA特征。由6种与铁死亡相关的lncRNA(PCAT6、MKLN1-AS、POLH-AS1、LINC00942、AL031985.3、LINC00942)构建的预后特征在肝癌患者中显示出有前景的临床预测价值。在训练集(p<0.001)和测试集(p = 0.024)中,高风险评分的患者比低风险评分的患者预后更差。进行主成分分析(PCA)和列线图以验证预后特征的价值。1年、3年和5年生存率的曲线下面积(AUC)分别为0.784、0.726、0.699。此外,TCGA显示,两个风险组之间的免疫细胞亚群及其相关功能存在显著差异,包括细胞溶解活性、MHC I类、I型和II型干扰素反应。两个风险组之间的免疫检查点如PDCD1、CTLA4、CD44、VTCN1也异常表达。这种基于与铁死亡相关lncRNAs的预后特征可能对肝癌患者的预后临床预测和免疫治疗反应具有前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf81/9033801/c7784f7dffa4/41598_2022_10508_Fig9_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cf81/9033801/4613c591ba7b/41598_2022_10508_Fig8_HTML.jpg
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