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鉴定和验证 17 个与调节性 T 细胞异质性相关的长链非编码 RNA,作为头颈部鳞状细胞癌的预后标志物。

Identification and Validation of 17-lncRNA Related to Regulatory T Cell Heterogeneity as a Prognostic Signature for Head and Neck Squamous Cell Carcinoma.

机构信息

Department of Otorhinolaryngology, Head and Neck Surgery, Yantai Yuhuangding Hospital, Qingdao University, Yantai, China.

Shandong Provincial Clinical Research Center for Otorhinolaryngologic Diseases, Yantai Yuhuangding Hospital, Yantai, China.

出版信息

Front Immunol. 2021 Nov 22;12:782216. doi: 10.3389/fimmu.2021.782216. eCollection 2021.

Abstract

Successful eradication of tumors by the immune system depends on generation of antigen-specific T cells that migrate to tumor sites and kill cancerous cells. However, presence of suppressive Treg populations inside tumor microenvironment hinders effector T cell function and decreases antitumor immunity. In this study we independently evaluated and confirmed prognostic signature of 17-Treg-related-lncRNA. Immune cell infiltration analysis using 17-lncRNA signature as a probe, accurately described Treg populations in tumor immune microenvironment. 17-lncRNA signature model predicted prognosis with excellent accuracy in all three cohorts: training cohort (AUC=0.82), testing cohort (AUC=0.61) and total cohort (AUC=0.72). The Kaplan-Meier analysis confirmed that the overall survival of patients in the low-risk group was significantly better than those in the high-risk group(P<0.001). CIBERSORT analysis confirmed that low risk group had higher infiltration of tumor killer CD8 T cells, memory activated CD4 T cells, follicular helper T cells and T cells regulatory (Tregs), and lower expression of M0 macrophages and Mast cells activated. These results indicate that the 17-lncRNA signature is a novel prognostic and support the use of lncRNA as a stratification tool to help guide the course of treatment and clinical decision making in patients at high risk of HNSCC.

摘要

免疫系统的成功消除肿瘤依赖于产生迁移到肿瘤部位并杀死癌细胞的抗原特异性 T 细胞。然而,肿瘤微环境中抑制性 Treg 群体的存在会阻碍效应 T 细胞的功能并降低抗肿瘤免疫力。在这项研究中,我们独立评估并证实了 17-Treg 相关长链非编码 RNA 的预后特征。使用 17-lncRNA 特征作为探针进行免疫细胞浸润分析,可准确描述肿瘤免疫微环境中的 Treg 群体。17-lncRNA 特征模型在三个队列中的预测预后均具有出色的准确性:训练队列(AUC=0.82)、测试队列(AUC=0.61)和总队列(AUC=0.72)。Kaplan-Meier 分析证实,低危组患者的总生存率明显优于高危组(P<0.001)。CIBERSORT 分析证实,低危组肿瘤杀伤性 CD8 T 细胞、记忆性激活 CD4 T 细胞、滤泡辅助性 T 细胞和 T 细胞调节性 Treg 的浸润更高,M0 巨噬细胞和 Mast 细胞激活的表达更低。这些结果表明,17-lncRNA 特征是一种新的预后标志物,并支持将长链非编码 RNA 用作分层工具,以帮助指导高危头颈部鳞状细胞癌患者的治疗过程和临床决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae13/8645855/249c23b64794/fimmu-12-782216-g001.jpg

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