Survival factors in lung cancer patients with mutations in the PROS1 , SERPINC1 , F2 , and F5 genes

Ryan Brownlee1, Aditya Birla1, Hung Bui1, Raniya Ahmad1, Dongyu Zhang1, Andrew Ji1 and Girindra Raval2 1 The Medical College of Georgia at Augusta University, Augusta, GA 30912, USA 2 Department of Medicine, Division of Hematology and Oncology, Medical College of Georgia at Augusta University, Augusta, GA 30912, USA Correspondence to: Ryan Brownlee, email:[email protected] Keywords: F5; PROS1; SERPINC1; lung cancer; thrombophilia Received: November 26, 2025 Accepted: August 05, 2026 Published: November 02, 2026 Copyright: © 2026 Brownlee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Purpose: Thrombophilia genes contribute to tumorigenesis and thrombotic events in lung cancer, yet current treatments do not incorporate gene-specific strategies for F2, F5, PROS1, and SERPINC1. We evaluated survival in lung cancer patients with thrombophilia mutations. Materials and Methods: We queried TCGA-LUAD and TCGA-LUSC for primary lung cancers with F2, F5, PROS1, or SERPINC1 mutations. STAR RNA-seq expression was included in univariate and multivariate Cox models comparing patients with versus without thrombophilia mutations, adjusting for age, race, AJCC stage, primary site, treatment type, laterality, and treatment modalities. Hazard ratios with 95% confidence intervals were calculated. Results: We identified 569 patients with thrombophilia mutations and 850 without. Across all mutations, higher pathologic stage and right-sided tumors were associated with worse survival. F5 mutations were significantly associated with survival in middle-lobe (HR 1.49, p = 0.028), pleural (HR 1.33, p = 0.006), and upper-lobe (HR 1.20, p = 0.025) cancers. SERPINC1 and PROS1 mutations were associated with improved survival in upper-lobe cancers. Among upper-lobe cancers, African American patients with F5 mutations had worse survival by age at diagnosis (HR 1.01, p = 0.015) and race (HR 1.33, p = 0.024). Conclusions: Thrombophilia mutations influence lung cancer survival and may help refine gene-targeted therapies.