| Popis: |
Background: In various malignant tumors, whether tumor mutational burden (TMB) was related to improving survival outcomes or promoting immunotherapy remained controversial. We aimed to study the prognosis of tumor mutation burden in cervical squamous cell carcinoma (CSCC) and its potential association with tumor-infiltrating immune cells.Methods: Transcriptome and somatic mutation profiles of CSCC were downloaded from the TCGA database. Somatic mutations were analyzed by "maftools" and visualized in waterfall plot. Then, TMB was calculated and we classified the samples into high-TMB and low-TMB groups based on the median data. Survival analysis and Wilcoxon test were used to investigate the prognostic value of TMB and its association with clinical variables. Differentially expressed genes (DEG) were identified in 2 TMN groups, and functional analysis was performed to find out significant biological pathways. Finally, we used the CIBERSORT algorithm to estimate the association between TMB and immune infiltration, and used the R package "vioplot" to visually draw the violin chart for each immune cell. Results: The data from TCGA were analyzed, and higher TMB levels conferred high overall survival time, associated with higher T staging (p = 0.048) and older age (p = 0.029). Then, the differential analysis determined 122 DEGs. And pathway research showed that the enrichment of TMB-related signature correlated with several cancer-related signaling pathways, including PI3K-Akt signaling pathway, Rap1 signaling pathway, MAPK signaling pathway and Ras signaling pathway. Through CIBERSORT package and Wilcoxon rank-sum test, T cells CD8 (p = 0.008), T cells CD4 memory activation (p = 0.002) and T cells follicular helper cells (p = 0.028) showed higher levels of infiltration in the high TMB group. However, T cells CD4 memory resting (p = 0.003) and T cells regulation (Tregs) (p = 0.033) showed lower levels of infiltration in the high TMB group. Conclusions: In summary, high TMB may inhibit the development of CSCC through anti-tumor immune cells. And our study might have some merits in elucidating the potential mechanism of TMB and immune infiltrates in CSCC and providing guidance of immunotherapy for endometrial cancer. |
