Downregulation of CCL22 and Mutation of NOTCH1 in Tongue Squamous Cell Carcinoma Decreases Th2 Cell Recruitment and Expression to Predict Poor Clinical Outcomes

Abstract

Background: Tongue squamous cell carcinoma (TSCC) exhibits a high rate of local recurrence and cervical lymph node metastasis. The effect of the tumor microenvironment on TSCC remains unclear.Methods: Transcriptome data and somatic mutation data of TSCC were obtained from the HNSC project of The Cancer Genome Atlas (TCGA). Immune filtration analysis between early stage (clinical stage I–II) and advanced stage (III–IV) was performed using single-sample Gene Set Enrichment Analysis and MCPcounter. Differentially expressed genes were filtered and their related functions were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Kaplan-Meier survival analysis and a Cox-regression model were used to evaluate the survival of patients with the CCL22 signature. Maftools was used to show an overview of somatic mutations in TSCC. Results: In patients with TSCC, Th2 cells were significantly increased in patients in the early stage of the disease. The Th2 cell-related chemokine CCL22 was downregulated in patients in the advanced stage. Univariate and multivariate Cox analyses revealed CCL22 as a good prognostic factor for TSCC. A nomogram based on the expression of CCL22 was constructed as a prognostic indicator for TSCC. NOTCH1 mutation was increased in patients in the advanced stage, which inhibited activation of the NOTCH1-Th2 differentiation pathway.Conclusions: In TSCC, high expression of CCL22 can promote the recruitment of Th2 cells and predict better survival. Mutation of NOTCH1 inhibits the differentiation of Th2 cells. Combined with decreased Th2 cell recruitment and differentiation, tumor progression may occur.