Association of BTRC rs10883617 with Survival Outcomes in Surgically Resected Non-Small Cell Lung Cancer

Abstract

Background/Objectives: Genetic variation in components of the ubiquitin–proteasome system may contribute to cancer progression and clinical outcomes. This study investigated whether potentially functional variants in E3 ubiquitin ligase-related genes are associated with survival outcomes after surgical resection of non-small cell lung cancer (NSCLC). Methods: The study included 744 Korean patients with stage I–IIIA NSCLC, divided into discovery and validation cohorts. Fifty-one potentially functional single-nucleotide polymorphisms in E3 ubiquitin ligase-related genes were evaluated for associations with overall survival (OS) and disease-free survival (DFS). Results: Among the polymorphisms examined, BTRC rs10883617 T>C was significantly associated with DFS in the validation cohort, whereas the association with OS showed a concordant trend but did not reach statistical significance. In the combined cohort, carriers of at least one C allele had significantly better OS (HR = 0.55, 95% CI = 0.34–0.90, p = 0.02) and DFS (HR = 0.64, 95% CI = 0.46–0.89, p = 0.01) than patients with the TT genotype. The C allele demonstrated significantly lower promoter activity than the T allele in A549 and H1299 lung cancer cell lines (both p < 0.01). BTRC mRNA expression was significantly higher in tumor tissues than in paired non-neoplastic tissues (p < 0.001), but did not differ by genotype. Conclusions: Collectively, BTRC rs10883617 T>C was associated with favorable survival outcomes and allele-specific promoter activity in surgically resected NSCLC. However, its effect on endogenous BTRC expression remains unconfirmed in this patient population. Independent external validation and further mechanistic studies are warranted.