A Complement and Coagulation Cascade-Related Prognostic Signature Predicts Survival and Immune Landscape in Lung Adenocarcinoma

Objective: To evaluate the prognostic value of complement and coagulation cascades (CCC) in lung adenocarcinoma (LUAD). Methods: Transcriptomic and clinical data of LUAD were retrieved from public databases. Differentially Expressed Genes (DEGs) were identified via the limma R package, and WGCNA was used to screen gene modules strongly correlated with CCC enrichment scores. Functional enrichment analysis was conducted with clusterProfiler. Univariate and LASSO Cox regression analyses were applied to build a CCC-related prognostic risk model, and its performance was validated using Kaplan–Meier survival analysis and ROC curves. ESTIMATE, MCPcounter, GSVA, and pRRophetic algorithms assessed immune infiltration and drug sensitivity, while CCK-8, Transwell, and scratch-healing assays verified the regulatory effects of biomarkers on cancer cells. Results: WGCNA identified brown modules that were significantly correlated with CCC scores; enrichment analysis showed that these genes mainly participated in NF-κB, B-cell receptor signaling, and T-cell differentiation pathways. Six key genes (CPS1, EPHB2, LARGE2, MS4A1, OAS3, S100P) were selected to construct the risk model, with the high-risk group exhibiting poorer overall survival and lower T/B-cell infiltration. Risk scores were positively correlated with Rapamycin and Phenformin IC50s but negatively correlated with FTI-277, BMS-509744, etc. EPHB2 inhibition suppressed lung cancer cell viability, migration, and invasion. Discussion: This study systematically characterized the molecular features and prognostic significance of CCC-associated genes in LUAD, established a CCC-related risk model, and confirmed their tight association with immune infiltration and drug sensitivity. Conclusion: The findings provide a theoretical foundation for precise prognostic evaluation and personalized treatment of LUAD.