Wang Weixi, Chang Guilin, Zhuo Ran, Ye Cong
Department of Geriatrics, Zhongshan Hospital, Fudan University, Shanghai, China.
Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
Front Genet. 2022 Nov 15;13:949457. doi: 10.3389/fgene.2022.949457. eCollection 2022.
Adrenocortical carcinoma (ACC) is an uncommon endocrine malignancy associated with poor clinical outcome. As a novel form of cell death, ferroptosis is reliant on the accumulation of iron and reactive oxygen species and is involved in the pathogenesis of various tumors, including ACC. Our study aimed to identify and characterize the prognostic ferroptosis-related lncRNA signature (FerRLSig) in ACC. A regulatory network of ferroptosis-related lncRNAs (FerRLs) and mRNAs was constructed based on The Cancer Genome Atlas (TCGA). Univariate and multivariate Cox regression assays were performed to construct the FerRLSig. Twenty-four FerRLs were identified in the prognostic model, and the high-risk FerRLSig was related to the worse overall survival (OS) in ACC [hazard ratio (HR): 1.936 (1.484-2.526), < 0.001]. The area under the curve (AUC) value of the FerRLSig was 0.936 according to the receiver operating characteristic (ROC) analyses, superior to other traditional clinicopathological features, further supported the utility in prognosis prediction of ACC. We further established a prognostic nomogram combining clinical factors with the FerRLSig, which showed favorable efficacy for survival prediction. Next, gene set enrichment analysis (GSEA) revealed that gene sets were involved in many immune regulatory biological processes related to malignancies. T-cell function of type II INF response and the immune checkpoints, including CD40, CD276, IDO2, NRP1, and CD80, were expressed with a significant difference between the low- and high-risk groups. This study offered new insights into the pathogenesis of ACC. The novel FerRLSig could be useful in predicting survival and may provide information of immunological research and treatment for ACC patients.
肾上腺皮质癌（ACC）是一种临床预后较差的罕见内分泌恶性肿瘤。作为一种新型细胞死亡形式，铁死亡依赖于铁和活性氧的积累，并参与包括ACC在内的各种肿瘤的发病机制。我们的研究旨在识别和表征ACC中与铁死亡相关的预后长链非编码RNA特征（FerRLSig）。基于癌症基因组图谱（TCGA）构建了铁死亡相关长链非编码RNA（FerRLs）和信使核糖核酸（mRNAs）的调控网络。进行单变量和多变量Cox回归分析以构建FerRLSig。在预后模型中鉴定出24个FerRLs，高危FerRLSig与ACC患者较差的总生存期（OS）相关[风险比（HR）：1.936（1.484 - 2.526），P < 0.001]。根据受试者工作特征（ROC）分析，FerRLSig的曲线下面积（AUC）值为0.936，优于其他传统临床病理特征，进一步支持其在ACC预后预测中的效用。我们进一步建立了一个将临床因素与FerRLSig相结合的预后列线图，该列线图在生存预测方面显示出良好的效果。接下来，基因集富集分析（GSEA）显示基因集参与了许多与恶性肿瘤相关的免疫调节生物学过程。II型干扰素反应的T细胞功能以及免疫检查点，包括CD40、CD276、IDO2、NRP1和CD80，在低风险组和高风险组之间表达存在显著差异。本研究为ACC的发病机制提供了新的见解。新型FerRLSig可用于预测生存，并可能为ACC患者提供免疫学研究和治疗信息。
