Tumor mutation burden (TMB) and Notch1 gene alteration are associated with short disease-free survival in early laryngocarcinoma.

e18049 Background: Patients with early-stage laryngocarcinoma, even stage T1-2N0, are at substantial risk of relapse and death. Molecular alterations are thought to be associated with the immune microenvironment in the tumor and to have an important role in predicting the prognosis. In this study, we explored the distinct features of molecular alterations and immune-related gene expression and examined the relationship between molecular alterations and prognosis. Methods: A total of 42 stage T1-2N0 laryngocarcinoma patients were enrolled, no patients received chemotherapy or immunotherapy before surgery, tissue samples from radical operation were collected. Of these, 23 cases developed disease progression within 24 months after operation [shorter disease-free survival (shorter DFS)], while others 19 cases showed longer DFS over 24 months (longer DFS). Distinct features of molecular alterations and immune-related gene expression in Formalin-fixed paraffin-embedded (FFPE) samples through using DNA sequencing and an immune oncology panel RNA sequencing platform were performed. Results: A total of 293 mutations were detected within 42 patients, the median number of mutations in the short-DFS group was higher than that in the long-DFS group (9.0 vs. 5.2; P = 0.045). No correlation between mutation type and DFS was found. TMB-high (Top 25%) was associated with worse DFS (TMB-L: Not reached, TMB-H: 11.5 months, p = 0.036; HR, 2.4; 95% CI 1.05 to 5.48). Among 522 cancer-related genes, alterations in 51 genes were detected. TP53 (33/42, 79%) was the most common mutation gene in the entire cohort. Mutations of LRP1B (30.4% vs 5.3%, p = 0.039) and Notch1 (21.7% vs 0%, p = 0.030) were significantly occurred in the short-DFS group, patients with Notch1 mutation had a significantly shorter DFS period (P = 0.0012). Univariate and multivariate analysis showed that high TMB and Notch1 mutation were independent prognostic factors in DFS. Conclusions: In early-stage laryngocarcinoma, Notch1 mutation and high TMB were associated in patients with short-DFS, indicating the potential prognostic biomarkers and therapeutic molecular targets for early-stage laryngocarcinoma.