Mutations in the Gene are a Prognostic Factor for Patients with Lung Squamous Cell Carcinomas.

PURPOSE

To analyze the relationship between titin () mutation gene and tumor mutational burden (TMB) and the with prognosis of lung squamous cell carcinomas (LUSC), and to explore the feasibility of as a potential prognostic marker of for LUSC.

METHODS

We analyzed the somatic mutation landscape of LUSC samples using datasets obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. Sequence data were divided into wild and mutant groups, and differences in TMB values between the groups compared using a Mann-Whitney -test. The Kaplan Meier method was used to analyze the correlation between mutation and LUSC prognosis, whereas CIBERSORT algorithm was used to calculate the degree of relative enrichment degree of among tumor-infiltrating lymphocytes in LUSC.

RESULTS

Analysis of both datasets revealed high mutations in the gene, with mutants exhibiting a significantly higher TMB value relative to the wild-type (P < 0.001). Prognosis of the TTN mutant group in LUSC was significantly better than that of wild-type (P = 0.009). Kaplan Meier curves showed that TTN mutation may be an independent prognostic factor in LUSC patients (HR: 0.64, 95% CI 0.48-0.85, P = 0.001), while GSEA analysis revealed that TTN mutation plays a potential role in the development of LUSC. Finally, analysis of LUSC immune microenvironment revealed that mutation was significantly associated with enrichment of macrophages M1 (p < 0.05).

CONCLUSION

mutation is associated with TMB, and is positively correlated with prognosis of LUSC. Therefore, this mutation may serve as a potential prognostic indicator of LUSC.