BRMS1 Expression in Surgically Resected Lung Adenocarcinoma Predicts Future Metastases and IsAssociated with a Poor Prognosis.

Abstract

Expression of breast cancer metastasis suppressor 1 gene (BRMS1) is decreased in NSCLC cells and tumors. We hypothesized that intratumoral breast cancer metastasis suppressor 1 (BRMS1) expression is associated with lung adenocarcinoma (LUAD) histologic subtypes and overall survival (OS) and disease-free survival (DFS) in patients undergoing resection for early-stage LUAD. Patients (N= 1030) who underwent complete resection for LUAD with tissue available for histologic evaluation were identified. Tissue microarrays were constructed, and immunostaining was performed and scored for intensity of BRMS1 expression. OS and DFS were estimated (by the Kaplan-Meier method) and compared between groups (by the log-rank test), stratified by stage. Hazard ratios (HRs) for hazard of death and recurrence were estimated using univariable and multivariable Cox proportional hazards models. OS and DFS nomograms were created, and model performance was examined. Intratumoral BRMS1 expression was high in 632 patients (61%) and low in 398 (39%). Low BRMS1 expression was associated with higher pathologic T stage (p= 0.001), larger tumor size (p ≤ 0.0001), greater lymphatic (p= 0.032) and vascular (p= 0.001) invasion, LUAD histologic subtype (p= 0.001), and intermediate and high architectural tumor grade (p= 0.003). Low BRMS1 expression was an independent predictor of worse OS (HR= 1.35, 95% confidence interval: 1.10-1.65, p= 0.004) and DFS (HR= 1.27, 95% confidence interval: 1.05-1.54, p= 0.012). OS and DFS nomograms showed excellent predictive performance based on discrimination and calibration. Among patients with surgically resected LUAD, OS and DFS were significantly worse in cases with low intratumoral BRMS1 expression. Our findings suggest that BRMS1 is an independent biomarker with prognostic significance in surgically resected LUAD.