Diagnostic and prognostic values of endothelial-cell-specific molecule-1 with malignant pleural effusions in patients with non-small cell lung cancer

Abstract

Over-expressed endothelial-cell-specific molecule-1 (ESM-1) in tumor vascular endothelium contributes to tumor angiogenesis, metastasis, and poor prognosis. However, the content of ESM-1 in pleural effusion is unclear. A retrospective study was carried out to investigate the diagnostic and prognostic values of ESM-1 with malignant pleural effusions in patients with non-small cell lung cancer (NSCLC). ESM-1 levels in malignant pleural effusion (MPE) from 70 patients with NSCLC and 50 cases of benign pleural effusion (BPE) were measured using enzyme-linked immunosorbent assay. Receiver operating characteristic (ROC) curve was calculated to assess the diagnostic value of ESM-1. Survival curves were performed by Kaplan-Meier method and survival characteristics were compared by log-rank test. Univariable and multivariate Cox proportional hazards model were carried out to analysis the significance of different prognostic factors for overall survival (OS). ESM-1 levels were significantly higher in MPE than those in BPE (p < 0.001). By ROC curve analysis, with a cutoff level of 19.58 ng/ml, the accuracy, sensitivity, and specificity for ESM-1 diagnosis MPE were 82.5%, 81.4%, and 84.0%, respectively. Moreover, NSCLC patients with pleural fluid ESM-1 levels below 19.58 ng/ml had significant longer OS than those patients with higher levels (22.09 months vs. 11.49 months, p = 0.003). Multivariate survival analysis showed that high MPE ESM-1 level was an independent prognostic factor (HR, 1.007; p = 0.039) for the OS of NSCLC patients. This study showed that ESM-1 level in pleural effusion could be a potential diagnostic and prognostic marker in NSCLC patients with MPE.

Keywords: ESM-1; biomarker; non-small cell lung cancer; overall survival (OS); prognosis.

Figure 1. The expression of ESM-1 in pleural effusion

MPE presents higher ESM-1 concentration than those with BPE (*p < 0.001).

Figure 2. Diagnostic value of pleural fluid ESM-1 level for NSCLC patients with MPE

The ROC curve discrimination of MPE and BPE according to pleural fluid ESM-1 concentrations (AUC = 0.884; 95% CI = 0.825–0.943) with a cutoff value of 19.58 ng/ml (sensitivity 81.4%; specificity 84.0%).

Figure 3. Kaplan-Meier survival curves for overall survival of NSCLC patients with different pleural fluid ESM-1 expression

The NSCLC patients with high ESM-1 expression had a significantly worse outcome compared with the patients with low ESM-1 expression (p = 0.003).