Predicting therapeutic responses in head and neck squamous cell carcinoma from TP53 mutation and The mutation of TP53 could be detected by cfDNA

Abstract

Objectives: Head and neck squamous cell carcinoma (HNSCC) was increasing globally. The mutation of the TP53 was the most common of all somatic genomic changes in HNSCC, and TP53 mutation was associated with the response of immunotherapeutic and chemotherapeutic. Tumor-derived circulating cell-free DNA (cfDNA) was minimally invasive method to determine genetic alterations for cancer. The study aimed to explore the therapeutic responses of TP53 mutation patients with HNSCC and the accuracy of cfDNA to detect TP53 mutation. Materials and methods: The information of TP53 mutations and patients’ survival time and clinical data in HNSCC was downloaded from The Cancer Genome Atlas (TCGA) Database. The difference of immune infiltration between TP53 mutant group and wild group was compared. The ssGSEA method applied to the transcriptome of HNSCC samples to assess the distribution of immune cell types between two groups. The chemotherapy response was constructed using the R software package, pRRophetic. GSEA enrichment analysis was performed based on TP53 mutation. The next-generation sequencing (NGS) was executed on cfDNA of 9 patients with HNSCC to detect genetic alterations. Tumor biopsy (n = 9) was sequenced using the same technique. Results: TP53 was the most frequently mutated gene in HNSCC. TP53 mutation was related to the immune cells and expression of immune-associated genes. The TP53 mutation group showed less response to immunotherapeutic but high sensitivity to some chemotherapies compared to wild-type group. TP53 was the most frequently mutated gene (6/9; 66.67%) in cfDNA. 27.27% of the tissue tumor variants were not detected in cfDNA when all TP53 mutations were considered. Conclusion: TP53 mutation could be used as a specific predictor of treatment response in patients with HNSCC. It was feasible to detect the TP53 mutations from HNSCC patients by cfDNA. The results suggested that the therapeutic response in patients could be predicted by detecting TP53 mutations in cfDNA, and large-scale and prospective studies were needed to validate it.