Genomic and immunological profiling reveals novel prognostic biomarkers for limited-stage small cell lung cancer.

Abstract

We aimed to investigate the genomic and immune microenvironmental characteristics and their prognostic value in limited-stage small cell lung cancer (SCLC). Whole exome sequencing and multiplex immunofluorescence analysis were conducted on 38 patients diagnosed with limited-stage SCLC. The two most frequently mutated cancer-related genes observed were RB1 (73.68%) and TP53 (63.16%). However, none of the cancer-related genes, including RB1 and TP53, were associated with prognosis. Furthermore, genomic factors such as tumor mutation burden, copy number instability, and mutant-allele tumor heterogeneity were unrelated to prognosis. Approximately 52.63% (20/38) of cases exhibited PD-L1 expression (combined positive score > 1). The average percentage of CD8-positive tumor-infiltrating lymphocytes (TILs) was 3.27%, with a range spanning from 0.04 to 18.96%. Survival analyses showed that PD-L1 positivity, a high proportion of CD8-positive TILs, and wild-type PI3K pathway were significantly associated with better survival. A predictive prognostic model was further developed based on these three biomarkers, resulting in more accurate stratification of patients according to disease-free survival (DFS, hazard ratio (HR) = 2.020, P < 0.001) and overall survival (OS, HR = 2.344, P < 0.001). Moreover, PD-L1 negative patients who did not undergo adjuvant chemotherapy exhibited significantly improved OS (P = 0.029) and a favorable trend in DFS (P = 0.053) compared to those who underwent adjuvant chemotherapy. In conclusion, this study analyzed the genomic and immune microenvironment characteristics of limited-stage SCLC and constructed a prognostic model based on PD-L1 expression, CD8-positive TILs, and PI3K pathway mutation, which may potentially contribute to the clinical management of limited-stage SCLC. Clinical trial number: Not applicable.