Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
J Thorac Oncol. 2018 Jan;13(1):73-84. doi: 10.1016/j.jtho.2017.10.006. Epub 2017 Oct 31.
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.
乳腺癌转移抑制因子 1 基因（BRMS1）的表达在非小细胞肺癌（NSCLC）细胞和肿瘤中降低。我们假设肿瘤内乳腺癌转移抑制因子 1（BRMS1）的表达与接受早期 LUAD 切除的患者的肺腺癌（LUAD）组织学亚型以及总生存期（OS）和无病生存期（DFS）相关。
确定了 1030 名接受 LUAD 完全切除术且组织可用于组织学评估的患者。构建组织微阵列，并进行免疫组织化学染色，对 BRMS1 表达强度进行评分。通过 Kaplan-Meier 方法（对数秩检验）估计 OS 和 DFS（按阶段分层），并比较各组之间的差异。使用单变量和多变量 Cox 比例风险模型估计死亡和复发风险的危险比（HR）。创建 OS 和 DFS 列线图，并检查模型性能。
632 例（61%）患者的肿瘤内 BRMS1 表达高，398 例（39%）患者的 BRMS1 表达低。BRMS1 低表达与较高的病理 T 分期（p=0.001）、更大的肿瘤大小（p≤0.0001）、更大的淋巴管（p=0.032）和血管（p=0.001）侵袭、LUAD 组织学亚型（p=0.001）以及中高结构肿瘤分级（p=0.003）相关。BRMS1 低表达是 OS（HR=1.35，95%置信区间：1.10-1.65，p=0.004）和 DFS（HR=1.27，95%置信区间：1.05-1.54，p=0.012）较差的独立预测因素。OS 和 DFS 列线图显示基于区分度和校准度的出色预测性能。
在接受手术切除的 LUAD 患者中，BRMS1 低表达的患者 OS 和 DFS 明显更差。我们的研究结果表明，BRMS1 是具有 LUAD 手术切除预后意义的独立生物标志物。
