Abstract
Small cell lung cancer (SCLC) is a highly malignant lung cancer subtype with a dismal prognosis and limited treatment options. This study aimed to identify new prognostic molecular biomarkers for SCLC and explore their immune-related implications for treatment strategies. We analyzed 200 SCLC samples via whole-exome sequencing (WES) and 313 samples by targeted sequencing. A smoking-related SBS4 mutational signature was linked to poorer prognosis and lower tumor mutational burden (TMB), while the APOBEC-mediated SBS13 signature was associated with better prognosis and higher TMB. We identified a molecular subtype with the worst outcomes and lowest TMB in both cohorts. Among 38 high-frequency mutated genes associated with SCLC prognosis, only UNC13A mutations were beneficial. Patients with UNC13A mutations had favorable immune infiltration and tumor immunogenicity. Additionally, TP53 splice site mutations were related to the worst survival outcomes. In conclusion, we discovered new molecular biomarkers for SCLC prognosis. Our findings on their immunological characteristics offer insights for developing novel SCLC treatment strategies.