Wu Pu, Shi Jinyuan, Wang Zhiyuan, Sun Wei, Zhang Hao
Department of Thyroid Surgery, The First Hospital of China Medical University, Shenyang, China.
Cancer Cell Int. 2022 Oct 10;22(1):307. doi: 10.1186/s12935-022-02722-8.
The functional alterations of eRNAs have been reported to be correlated with tumorigenesis. However, the roles of eRNAs in thyroid cancer (THCA) remain still unclear. This study aimed to construct an immune-related eRNA prognostic signature that could effectively predict the survival and prognosis for THCA.
The Weighted Gene Co-Expression Network Analysis (WGCNA) was performed to identify THCA-specific immune-related hub genes and immune-related eRNAs were obtained using Pearson correlation analysis. Univariate and least absolute shrinkage and selection operator (LASSO) Cox regression were conducted to construct an immune-related eRNA prognostic signature in training cohort, and the predictive capability was verified in test cohort and entire cohort. Kaplan-Meier analysis, principal component analysis (PCA), receiver operating characteristic (ROC) curves, and nomogram were used to validate the risk signature. Furthermore, CIBERSORT, ESTIMATE and ssGSEA were analyzed to explore the tumor immune microenvironment (TIME) of the risk signature, and the response of potential immunotherapeutic were also discussed.
A total of 125 immune-related eRNAs were obtained and 16 immune-related eRNAs were significantly correlated with overall survival (OS). A 9-immune-related eRNA prognostic signature was constructed, and the risk score was identified as an independent predictor. High-risk groups were associated with a poorer OS. Immune microenvironment analysis indicated that low risk score was correlated with higher immuneScore, high immune cell infiltration, and the better response of immunotherapy. Additionally, we also detected 9 immune-related eRNA expression levels in sixty-two matched tumorous and non-tumorous tissues using qRT-PCR analysis.
Our immune-related eRNA risk signature that was an independent prognostic factor was strongly correlated with the immune microenvironment and may be promising for the clinical prediction of prognosis and immunotherapeutic responses in THCA patients.
据报道，增强子RNA（eRNAs）的功能改变与肿瘤发生相关。然而，eRNAs在甲状腺癌（THCA）中的作用仍不清楚。本研究旨在构建一种免疫相关的eRNA预后特征，以有效预测THCA的生存和预后。
进行加权基因共表达网络分析（WGCNA）以识别THCA特异性免疫相关枢纽基因，并使用Pearson相关分析获得免疫相关eRNAs。在训练队列中进行单因素和最小绝对收缩和选择算子（LASSO）Cox回归以构建免疫相关的eRNA预后特征，并在测试队列和整个队列中验证预测能力。使用Kaplan-Meier分析、主成分分析（PCA）、受试者工作特征（ROC）曲线和列线图来验证风险特征。此外，分析CIBERSORT、ESTIMATE和ssGSEA以探索风险特征的肿瘤免疫微环境（TIME），并讨论潜在免疫治疗的反应。
共获得125个免疫相关eRNAs，其中16个免疫相关eRNAs与总生存期（OS）显著相关。构建了一个包含9个免疫相关eRNAs的预后特征，并将风险评分确定为独立预测因子。高风险组的OS较差。免疫微环境分析表明，低风险评分与较高的免疫评分、高免疫细胞浸润以及更好的免疫治疗反应相关。此外，我们还使用qRT-PCR分析检测了62对配对的肿瘤组织和非肿瘤组织中9个免疫相关eRNAs的表达水平。
我们的免疫相关eRNA风险特征是一个独立的预后因素，与免疫微环境密切相关，可能对THCA患者的预后临床预测和免疫治疗反应具有重要意义。
