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

Abstract

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 are GTF2I (0.4263 [0.3590; 0.4936]), TP53 (0.1101 [0.0000; 0.2586]), and RAS (0.0341 [0.0104; 0.0710]), and TP53 (0.1797 [0.0732; 0.3203]), CDKN2A (0.0608 [0.0139; 0.1378]), and TET2 (0.0318 [0.0087; 0.0639]), respectively. A uniform GTF2I mutational rate in thymomas and TP53 mutational 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.