­­Prognostic analysis of tumor mutation burden combined with immune infiltration of Thymic epithelial tumors

Abstract

Background: Thymic epithelial tumors (TETs) are uncommon neoplasms with poor prognosis and limited effective therapeutic options. This study aims to investigate the prognosis of tumor mutation burden (TMB) and the potential association with immune infiltrates in TETs. Methods: Tumor mutation burden (TMB) was calculated using Maftools package and the samples were classified into high-TMB and low- TMB groups. Differentially expressed genes (DEGs) combined with immune cell infiltration and survival rate were analyzed between the low-TMB and high-TMB groups.Results: Single nucleotide polymorphism (SNP) occurred more frequently than insertion or deletion, and C>T was the most common single nucleotide variants (SNV) in TETs. The results of Kaplan–Meier curve indicated that a high TMB was associated with worse clinical outcomes of TETs. Moreover, 3 hub immune genes associated with immune infiltration were significantly associated with prognosis. Besides, the TMB-related signature (TMBRS) model based on the three hub immune genes possessed good predictive value with area under curve (AUC) 0.729, and patients with higher TMBRS scores showed worse TETs outcomes. In addition, infiltration levels of native CD4+ T cell, activated memory CD4+ T cell and follicular helper T cells in low-TMB group were higher than those in high-TMB group, which were correlated positively with prognosis of TETs. Conclusion: TETs patients with low TMB have better prognosis than those with high TMB, and TMB might affect the development of TETs by regulating immune infiltration.