Mutation-associated transcripts reconstruct the prognostic features of tongue squamous cell carcinoma

Tongue squamous cell carcinoma is highly malignant with a poor prognosis. This study aimed to combine whole-genome sequencing, whole-genome methylation, and whole transcriptome analyses to better understand the molecular mechanisms of this cancer. Cancerous and paraneoplastic tissues from five patients with tongue squamous cell carcinoma were included as five paired samples. After multi-omics sequencing, differentially methylated intervals, methyl loop sites, methylated promoters, and transcripts were screened for variation in all paired samples. Correlations between them were analyzed to determine biological processes in tongue squamous cell carcinoma. We found five mutated methylation promoters that were significantly associated with the expression levels of mRNAs and lncRNAs. Functional annotation of these transcripts revealed their involvement in triggering the mitogen-activated protein kinase cascade, which is associated with cancer progression and the development of drug resistance during treatment. The prognostic signature models constructed based on the WDR81 and HNRNPH1 genes and combined clinical phenotype-gene prognostic signature models have shown high predictive efficacy and can be applied to predict patient prognostic risk in clinical settings. We identified biological processes in tongue squamous cell carcinoma that are initiated by mutations in the methylation promoter and are associated with the expression levels of specific mRNAs and lncRNAs. Ultimately, changes in the transcript levels affect the prognosis of tongue squamous cell carcinoma patients.