Identification and characterization of shared transcriptomic signatures in BRCA2-mutated metastatic breast cancer and...

Breast cancer and lung adenocarcinoma (LUAD) are most prevalent forms of malignancies worldwide and are associated with BRCA2 variants. While BRCA2 pathogenic variants are well established in breast cancer, their transcriptional consequences in lung adenocarcinoma remain poorly characterized, and no study has directly compared the shared differentially expressed gene (DEG) signature between BRCA2-variant metastatic breast cancer and BRCA2-variant LUAD. In this study, we used an integrative bioinformatics approach to identify and characterize this shared transcriptomic profile using publicly available TCGA and GEO datasets accessed via cBioPortal. Top dysregulated genes were subjected to protein-protein interaction (PPI) analysis using STRING and Cytoscape (CytoHubba, MCC algorithm), functional enrichment through Metascape and survival analysis through UALCAN, with disease associations validated against the DISEASES database. SERPINA1, PIGR, FGG and FCGBP were identified as candidate hub genes, common in both types of malignancies. The breast cancer gene set was associated with impaired BRCA2-RAD51-mediated homologous recombination, and the lung dataset had strong signatures of alveolar type 2 (AT2) cells and signatures specific to lung adenocarcinoma (LUAD). SERPINA1 and PIGR were significant markers in breast cancer and FGG was significant marker in LUAD. The findings identify a partially overlapping epithelial transcriptional profile associated with BRCA2-variant breast and lung tumor datasets. However, these observations represent associations within BRCA2-altered cohorts and do not establish that BRCA2 dysfunction directly drives the identified transcriptional changes. SERPINA1, PIGR, FGG, and FCGBP therefore represent candidate tissue-dependent biomarkers requiring independent validation.