ArticleDiscover oncology2025
Genomic and immunological profiling reveals novel prognostic biomarkers for limited-stage small cell lung cancer.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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.
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