Abstract
ObjectiveTo explore the mutated genes in esophageal cancer (ESCA), and evaluate its relationship with tumor mutation burden (TMB) and prognosis of ESCA, and analyze the advantages of FAT3 as a potential prognostic marker in ESCA.MethodsThe somatic mutation landscape was analyzed according to ESCA samples from the TCGA and ICGC database. The differences of TMB between mutant type and wild type of frequently mutated genes were compared by Mann-Whitney U test. The association of gene mutations with prognosis was analyzed by Kaplan-Meier method. The relative abundance of 22 tumor-infiltrating lymphocyte subsets in ESCA was calculated by CIBERSORT algorithm.ResultsFAT3 was a high frequency mutation in both TCGA and ICGC samples from the somatic mutation landscape. Then, the mutation type of FAT3 had significantly higher TMB in patients with ESCA compared the wild type (P<0.05). Meanwhile, the prognosis of FAT3 mutation type was significantly worse in patients with ESCA(P<0.05), and the FAT3 mutation status might be an independent factor for prognosis of patients with ESCA (HR: 1.262–5.922, P=0.011). The GSEA analysis revealed the potential mechanism of FAT3 mutation on the occurrence and development of ESCA. Finally, naive B cells were significantly enriched in FAT3 mutation samples of the ESCA microenvironment (P<0.05).ConclusionsFAT3 mutation is related to TMB and poor prognosis in ESCA. FAT3 mutation may be a prognostic marker of ESCA, and reveal the potential mechanism of FAT3 mutation on ESCA.
Highlights
Esophageal cancer (ESCA) is a common malignant tumor of the digestive tract in the world
For mutant genes with significantly higher Tumor mutation burden (TMB), we conducted survival analysis and found that the prognosis of CSMD1, FAT3, and LRP1B mutation type were significantly worse in patients with ESCA (P
Research has shown that TMB may be a potential marker for predicting the efficacy of immunotherapy [18]; we explored the relationship between FAT3 mutation and tumorinfiltrating immune in ESCA
Summary
Esophageal cancer (ESCA) is a common malignant tumor of the digestive tract in the world. It has the characteristics of high malignancy and poor prognosis. ESCA is mainly characterized by progressive dysphagia, and most patients diagnosed with esophageal cancer have entered the advanced stage. Tumor cells can produce many specific mutations at the genetic level, and every 150 non-synonymous mutations may produce one to two neoantigens, which can be recognized by the autoimmune system, activating T cells and causing immune response [6,7,8]. The more non-synonymous mutations, the more neoantigens will be recognized by the autoimmune system, and the stronger the autoimmune effect can be caused. Several clinical studies have demonstrated that TMB can predict the efficacy of immunotherapy for solid tumors, such as melanoma [11], bladder cancer [12], and small cell lung cancer [13]
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