Construction of a novel tumor mutation burden-related mRNA signature for prognosis prediction in laryngeal squamous cell carcinoma.

Laryngeal squamous cell carcinoma (LSCC) is a common cancer with high mortality and tumor mutation burden (TMB), and high TMB is associated with favorable survival. The expression, mutation, and survival data were obtained from The Cancer Genome Atlas database. The mutation and differentially expressed genes were analyzed using limma R package. The function enrichment was analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. TMB-related genes were identified by Weighted correlation network analysis. Univariate, multivariate and Lasso cox analyses were used to determine hub genes. The risk model and mRNA expression was validated by Receiver Operating Characteristic curve and qRTPCR. The immune infiltration was analyzed by xCELL. The drug sensitivity was determined through gene set cancer analysis database. We identified 1129 differentially expressed genes related to TMB. Enrichment analysis showed they were associated with immune response. ANKLE1 and PPP1R14A were screened out as hub genes. Receiver Operating Characteristic curve identified that the risk model had an effective prognosis value in progression-free interval of LSCC. Immune infiltration levels of 16 immune cells were significantly changed in high risk score group compared with low risk score group. ANKLE1 and PPP1R14A expressions were significantly upregulated in tumor group, which was consistent with qRTPCR results, and associated with better prognosis. ANKLE1 was negatively related to many drug sensitivities, while PPP1R14A was positively related to some drug sensitivities. We constructed an effective risk model constructed by ANKLE1 and PPP1R14A which was related to TMB in LSCC.