Fibrinogen beta chain as a prognostic biomarker and therapeutic target in tobacco-associated lung adenocarcinoma

The β-subunit of fibrinogen (FGB), a key element of the main plasma clotting protein, is increasingly recognised as a contributor to tumour biology. To clarify its relevance in smoking-related lung adenocarcinoma (LUAD), we interrogated seven public transcriptomic cohorts obtained from the TCGA portal on UCSC-Xena and from the GEO repository, together with their matched clinical annotations. Across datasets, patients with a history of smoking displayed markedly higher FGB transcript levels than never-smokers. Greater FGB abundance correlated with worse Eastern Cooperative Oncology Group (ECOG) performance status and more advanced TNM classification. Genotype-stratified analysis showed reduced FGB expression in EGFR-mutant LUAD, whereas KRAS- or STK11-mutant tumours exhibited the opposite pattern. Kaplan-Meier curves indicated that high FGB expression predicted inferior overall survival (OS) and progression-free survival (PFS); this unfavourable prognostic effect remained evident when analyses were restricted to smokers. In multivariable Cox models, FGB emerged as an independent determinant of outcome for tobacco-exposed LUAD. A prognostic nomogram combining FGB expression with TNM stage outperformed TNM stage alone and yielded a clear net clinical benefit. Pathway enrichment pointed towards coagulation-associated processes as the principal biological context for FGB up-regulation. Collectively, these findings identify elevated FGB as a hallmark of an aggressive smoker-derived LUAD subset and as a standalone prognostic biomarker, offering potential value for risk stratification and therapeutic decision-making in this patient population.