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构建免疫相关 LncRNAs 分类器以预测胸腺上皮肿瘤预后和免疫治疗反应

英文原题:Construction of immune-related LncRNAs classifier to predict prognosis and immunotherapy response in thymic epithelial tumors.

查看英文原题

Construction of immune-related LncRNAs classifier to predict prognosis and immunotherapy response in thymic epithelial tumors.

PubMed 2022/05/27(内容时间) Biosci Rep Q2 · IF 4.5(JCR 2025)

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中文摘要

本研究旨在构建免疫相关长链非编码RNA(IRL)分类器,以准确预测胸腺上皮肿瘤(TET)患者的预后和免疫治疗应答。基于单变量Cox回归和Lasso回归,筛选出6种与预后相关的IRL(AC004466.3、AC138207.2、AC148477.2、AL450270.1、HOXB-AS1和SNHG8),并据此构建分类器。qRT-PCR验证结果显示,与正常对照相比,TET样本中AC138207.2、AC148477.2、AL450270.1和SNHG8表达较高,而AC004466.3和HOXB-AS1表达较低。IRL分类器能够根据不同生存指标有效地将患者划分为低危组和高危组;在预测能力和临床应用价值方面,该分类器优于Masaoka分期系统。

此外,IRL分类器与TET中的免疫细胞浸润(尤其是树突状细胞、活化记忆CD4 T细胞、TIL和T细胞亚群)、免疫微环境(免疫评分和免疫检查点抑制剂相关指标)及免疫原性(肿瘤突变负荷,TMB)显著相关,提示该分类器与免疫特征密切相关,可能帮助为TET患者选择更有效的免疫治疗策略。令人鼓舞的是,根据TIDE算法,IRL低危亚组中免疫治疗应答者更多,且IRL评分与免疫治疗应答呈稳定负相关。

总之,本研究建立的IRL分类器可用于预测TET患者预后、免疫浸润状态和免疫治疗应答,并可能有助于制定个体化免疫治疗建议。

展开英文摘要原文

The primary objective of this study was to construct an immune-related long noncoding RNAs (IRLs) classifier to precisely predict the prognosis and immunotherapy response of patients with thymic epithelial tumors (TET). Based on univariable Cox regression analysis and Lasso regression, six prognosis-related IRLs (AC004466. 3, AC138207. 2, AC148477. 2, AL450270. 1, HOXB-AS1 and SNHG8) were selected to build an IRL classifier.

Importantly, results of qRT-PCR validated that higher expression levels of AC138207. 2, AC148477. 2, AL450270. 1 and SNHG8 as well as lower expression levels of AC004466. 3, and HOXB-AS1 in TETs samples compared with normal controls. The IRL classifier could effectively classify patients into the low-risk and high-risk groups based on the different survival parameters. In terms of predictive ability and clinical utility, the IRL classifier was superior to Masaoka staging system.

Additionally, IRL classifier is significantly associated with immune cells infiltration (dendritic cells, activated CD4 memory T cells and tumor-infiltrating lymphocyte (TIL), T cell subsets in particular), immune microenvironment (immune score and immune checkpoint inhibitors) and immunogenicity (TMB) in TETs, which hints that IRL classifier is tightly correlated with immune characteristics and might guide more effective immunotherapy strategies for TETs patients.

Encouragingly, according to TIDE algorithm, there were more immunotherapy responders in the low-risk IRL subgroup and the IRL score was robustly negatively linked to the immunotherapeutic response. To sum up, the IRL classifier was established, which can be used to predict the prognosis, immune infiltration status, immunotherapy response in TETs patients, and may facilitate personalized counseling for immunotherapy.

论文信息

作者
Su Y、Ou Y、Chen Y、Ma X
第一作者单位
Department of Thoracic Surgery, Sanya Central Hospital, Sanya, 572000, Hainan Province, PR China.China
通讯作者单位
Department of Thoracic Surgery, Haikou People's Hospital, Haikou 570208, Hainan Province, PR China.China
期刊
Bioscience reports2022 May 27
原文标识
PubMed 35438133 · DOI 10.1042/BSR20220317