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.

Highlights

  • Lung cancer is the leading cause of cancer-related death in the world [1], and non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases [2]

  • We evaluated the levels of endothelial-cell-specific molecule-1 (ESM-1) in NSCLC patients with malignant pleural effusion (MPE) and benign pleural effusion (BPE) controls

  • Our results showed that the levels of pleural fluid ESM-1 were significantly increased in MPE than those in BPE controls

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Summary

Introduction

Lung cancer is the leading cause of cancer-related death in the world [1], and non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases [2]. Malignant pleural effusion (MPE) is a common complication in NSCLC patients and an independent factor for poor survival [3]. Since the treatment and prognosis are different, it is important to distinguish MPE from benign pleural effusion (BPE) to plan appropriate management. Several approaches including thoracocentesis, closed pleural biopsy, and thoracoscopy have been used to obtain the pleural effusion for the cytologic or histologic diagnosis. If cytology is negative, tumor biomarkers in pleural effusion such as carcinoembryonic antigen (CEA), cytokeratin 19 fragments (CYFRA 21-1) and carbohydrate antigen 153 (CA153) can be used for the identification of those patients with a high clinical suspicion for malignancy [4,5,6]. It is essential to search more accurate non-invasive biomarkers for the differential diagnosis of pleural effusion

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