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白细胞介素-13 受体 α2 基因表达是肾上腺皮质癌患者不良预后的生物标志物。

IL-13Rα2 gene expression is a biomarker of adverse outcome in patients with adrenocortical carcinoma.

机构信息

Division of Cellular and Gene Therapies, Tumor Vaccines and Biotechnology Branch, Center for Biologics and Evaluation Research, US Food and Drug Administration, Silver Spring, Maryland, United States of America.

Department of Zoology, Chaudhary Charan Singh University, Meerut, Uttar Pradesh, India.

出版信息

PLoS One. 2021 Feb 16;16(2):e0246632. doi: 10.1371/journal.pone.0246632. eCollection 2021.

Abstract

Adrenocortical carcinoma (ACC) is a rare but aggressive endocrine malignancy that usually results in a fatal outcome. To allow the better clinical management and reduce mortality, we searched for clinical and molecular markers that are reliable predictor of disease severity and clinical outcome in ACC patients. We determined a correlation between the overexpression of IL-13Rα2 and the clinical outcome in ACC patients using comprehensive data available in The Cancer Genome Atlas (TCGA) database. The dataset of 79 ACC subjects were divided into groups of low, medium, or high expression of IL-13Rα2 as determined by RNA-seq. These patients were also stratified by length of survival, overall survival, incidence of a new tumor event, incidence of metastasis, and production of excess hormones. We report a correlation between IL-13Rα2 expression and survival of subjects with ACC. High expression of IL-13Rα2 in ACC tumors was significantly associated with a lower patient survival rate and period of survival compared to low expression (p = 0.0084). In addition, high IL-13Rα2 expression was significantly associated with a higher incidence of new tumor events and excess hormone production compared to low or medium IL-13Rα2 expression. Within the cohort of patients that produced excess hormone, elevated IL-13Rα2 expression was significantly associated with a lower survival rate. Additionally, IL-13Rα1 had a potential relationship between transcript level and ACC survival. Our results and promising antitumor activity in preclinical models and trials indicate that IL-13Rα2 expression is an important prognostic biomarker of ACC disease outcome and a promising target for therapeutic treatment of ACC.

摘要

肾上腺皮质癌 (ACC) 是一种罕见但具有侵袭性的内分泌恶性肿瘤,通常导致致命结局。为了更好地进行临床管理并降低死亡率,我们寻找了可可靠预测 ACC 患者疾病严重程度和临床结局的临床和分子标志物。我们使用癌症基因组图谱 (TCGA) 数据库中提供的综合数据,确定了 IL-13Rα2 的过表达与 ACC 患者的临床结局之间的相关性。在 79 名 ACC 患者的数据集根据 RNA-seq 确定 IL-13Rα2 的低、中或高表达,将这些患者也按生存时间、总生存、新发肿瘤事件发生率、转移发生率和激素过量产生进行分层。我们报告了 IL-13Rα2 表达与 ACC 患者生存之间的相关性。与低表达相比,ACC 肿瘤中 IL-13Rα2 的高表达与患者生存率和生存时间降低显著相关(p = 0.0084)。此外,与低或中 IL-13Rα2 表达相比,IL-13Rα2 的高表达与新发肿瘤事件和激素过量产生的发生率更高显著相关。在产生激素过量的患者队列中,IL-13Rα2 的高表达与生存率降低显著相关。此外,IL-13Rα1 与 ACC 生存之间存在潜在的转录水平关系。我们的结果以及临床前模型和试验中的有希望的抗肿瘤活性表明,IL-13Rα2 表达是 ACC 疾病结局的重要预后生物标志物,是 ACC 治疗的有前途的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8a5b/7886164/43966d72d208/pone.0246632.g001.jpg

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