文章：

胸腺上皮肿瘤的遗传变异与分子景观描绘：一项系统综述与荟萃分析

Depiction of the Genetic Alterations and Molecular Landscapes of Thymic Epithelial Tumors: A Systematic Review and Meta-Analysis

原文发布日期：25 August 2024

DOI: 10.3390/cancers16172966

类型: Article

开放获取: 是

英文摘要：

Thymic epithelial tumors (TETs), consisting of thymomas, thymic carcinomas (TCs), and thymic neuroendocrine tumors, are rare diseases. Surgery remains the prime option in resectable and early-stage TETs, while chemotherapy, targeted therapy, and immunotherapy are also potential treatment modalities. However, the inadequate comprehension of the molecular landscape of TETs impedes the exploitation of such therapies. Hence, we conducted a meta-analysis which includes 21 studies reporting on genomic alterations in TETs and 14 studies reporting on PD-L1 expression levels, respectively. The pooled estimated rates of the most frequently mutated genes and PD-L1 expression levels were analyzed using the R software. We uncovered that the pooled estimated overall mutation rate is 0.65 ([0.49; 0.81]), and the top three genes with highest mutation frequency in thymomas and TCs areGTF2I(0.4263 [0.3590; 0.4936]),TP53(0.1101 [0.0000; 0.2586]), andRAS(0.0341 [0.0104; 0.0710]), andTP53(0.1797 [0.0732; 0.3203]),CDKN2A(0.0608 [0.0139; 0.1378]), andTET2(0.0318 [0.0087; 0.0639]), respectively. A uniformGTF2Imutational rate in thymomas andTP53mutational rate in thymic squamous cell carcinomas (TSCCs) are also observed. The pooled estimated expression level of PD-L1 is 0.71 ([0.59–0.81]). This systematic review provides an overview of the gene alteration landscape and PD-L1 expression levels in TETs, discovers several potential confounding factors that may contribute to the high heterogeneity, and facilitates deeper investigations into the elucidation of the molecular landscape of TETs.

摘要翻译： 

胸腺上皮肿瘤（TETs）包括胸腺瘤、胸腺癌（TCs）和胸腺神经内分泌肿瘤，属于罕见疾病。对于可切除及早期TETs，手术仍是主要治疗选择，而化疗、靶向治疗及免疫治疗亦为潜在治疗手段。然而，目前对TETs分子特征的认识不足，限制了这些疗法的有效应用。为此，我们开展了一项荟萃分析，共纳入21项关于TETs基因组变异的研究和14项关于PD-L1表达水平的研究。使用R软件对高频突变基因的合并估计率及PD-L1表达水平进行分析。结果显示：总体合并突变率为0.65（[0.49; 0.81]）；胸腺瘤中突变频率最高的三个基因依次为GTF2I（0.4263 [0.3590; 0.4936]）、TP53（0.1101 [0.0000; 0.2586]）和RAS（0.0341 [0.0104; 0.0710]），胸腺癌中则为TP53（0.1797 [0.0732; 0.3203]）、CDKN2A（0.0608 [0.0139; 0.1378]）和TET2（0.0318 [0.0087; 0.0639]）。研究同时观察到胸腺瘤中GTF2I突变率及胸腺鳞状细胞癌（TSCCs）中TP53突变率具有一致性特征。PD-L1的合并表达水平为0.71（[0.59–0.81]）。本系统综述全面梳理了TETs的基因变异特征与PD-L1表达水平，揭示了可能导致高度异质性的潜在混杂因素，为深入解析TETs分子图谱提供了重要参考。

原文链接：

Depiction of the Genetic Alterations and Molecular Landscapes of Thymic Epithelial Tumors: A Systematic Review and Meta-Analysis