Characteristics of GTF2I L424H Mutated Thymoma and its Prognostic Impact: A Comprehensive Study

Thymic Epithelial Tumor (TET), a rare thoracic tumor, including thymoma and thymic carcinoma, has limited research on thymoma prognostic markers compared to thymic carcinoma. Using the cBiportal database, we analyzed gene expression, methylation, and mutation data in TETs. We explored the relationship between the GTF2I L424H mutation and thymoma pathology through differential gene expression, pathway enrichment analyses, and COX regression to develop a thymoma risk score. Compared with GTF2I wild-type, patients harboring GTF2I L424H mutation displayed distinctive gene expression and methylation profiles, resembling differences between pathology low-risk and high-risk patients. Importantly, patients with the GTF2I L424H mutation demonstrated a better prognosis than wild-type patients, but no such distinction was noted between low-risk and high-risk patients. Pathway analysis suggested that the mutation potentially regulates tumor development-related pathways, including the P53, Hippo, and TGFβ signaling pathways, ECM-receptor interaction, and tumor immune cell infiltration. Additionally, ten hub genes identified by cytoHubba, FGF20 , FGF10 , EGF , and TWIST1 were selected by stepwise multivariate Cox regression to construct a risk score model for thymoma. These findings highlight the potential role of the GTF2I L424H mutation as a prognostic factor, advocating for genetic profiling in personalized treatment strategies.