| Popis: |
Tumor mutation burden (TMB), an emerging molecular determinant, is accompanied by microsatellite instability and immune infiltrates in various malignancies. However, whether TMB is related to the prognosis or immune responsiveness of adrenocortical carcinoma (ACC) remains to be elucidated. This paper aims to investigate the impact of TMB on the prognosis and immune microenvironment infiltration in ACC. The somatic mutation data, gene expression profile, and corresponding clinicopathological information were retrieved from TCGA. The mutation landscape was summarized and visualized with the waterfall diagram. The ACC patients were divided into low and high TMB groups based on the median TMB value and differentially expressed genes (DEGs) between the two groups were identified. Diverse functional analyses were conducted to determine the functionality of the DEGs. The immune cell infiltration signatures were evaluated based on multiple algorithms. Eventually, a TMB Prognostic Signature (TMBPS) was established and its predictive accuracy for ACC was evaluated. Single nucleotide polymorphism and C > T were found to be more common than other missense mutations. In addition, lower TMB levels indicated improved survival outcomes and were correlated with younger age and earlier clinical stage. Functional analysis suggested that DEGs were primarily related to the cell cycle, DNA replication, and cancer progression. Additionally, significant differences in infiltration levels of activated CD4+ T cells, naive B cells, and activated NK cells were observed in two TMB groups. We also found that patients with higher TMBPS showed worse survival outcomes, which was validated in the Gene Expression Omnibus database. Our study systematically analyzed the mutation and identified a TMBPS combined with immune microenvironment infiltration in ACC. It is expected that this paper can promote the development of ACC treatment strategies. |
