Clinical significance of angiopoietin-like protein 4 expression in tissue and serum of esophageal squamous cell carcinoma patients

Jun Yi,Hai-Zhu Song,Lei Xiong,Ban-Zhou Pan

doi:10.1007/s12032-013-0680-y

Abstract

Angiopoietin-like protein 4 (ANGPTL4) has been reported to promote tumor growth, metastasis, and angiogenesis under certain conditions. The aim of this study was to examine ANGPTL4 expression in tumor and serum tissues from esophageal squamous cell carcinoma (ESCC) patients. A total of 78 ESCC patients treated with radical resection were enrolled in this study. Immunohistochemistry was used to detect ANGPTL4 expression in ESCC tissues. Serum ANGPTL4 levels were determined via enzyme-linked immunosorbent assay (ELISA). The receiver operating characteristics curve was constructed to describe diagnostic specificity and sensitivity. There were 52 cases (69.2 %) showing a higher level of ANGPTL4 expression in tumor tissues than that in normal tissues, and the rate of ANGPTL4 protein high/moderate expression in ESCC and normal tissues was 55.1 % (43/78) and 6.4 % (5/78), respectively, with a significant difference (P < 0.001). Moreover, the high/moderate of ANGPTL4 protein was significantly associated with lymph metastasis, clinical stage, and adverse 2-year progression-free survival. In addition, serum ANGPTL4 level in ESCC patients was much higher than that in patients with benign esophageal disease (P < 0.001), and area under the curve was 0.94 (95 % CI 0.886390–0.978173, P < 0.001). But serum ANGPTL4 level was significantly decreased at post-operative 7–10 days (P = 0.004). ANGPTL4 upregulation may play an important role in ESCC development, and serum ANGPTL4 level may be a potential tumor marker for ESCC diagnosis and prognosis.

Highlights

Esophageal squamous cell carcinoma (ESCC) comprises the majority of esophageal cancer in China and is characterized by both high morbidity and high mortality [1]
Serum Angiopoietin-like protein 4 (ANGPTL4) levels in most esophageal squamous cell carcinoma (ESCC) patients were decreased after 7–10 days of surgery, and the pre-/post-operative concentrations were 202.44 ± 131.03 ng/mL and 128.73 ± 69.49 ng/mL, respectively (P = 0.004)
In concordance with the results of Shibata et al [10], we found that the level of ANGPTL4 protein expression in ESCC was much higher than that in matched normal tissues, and an elevated expression of ANGPTL4 protein was significantly associated with lymph metastasis, clinical stage, and adverse 2-year progression-free survival (PFS), further confirming the important roles of ANGPTL4 dysfunction in ESCC development in Chinese population

Summary

Introduction

Esophageal squamous cell carcinoma (ESCC) comprises the majority of esophageal cancer in China and is characterized by both high morbidity and high mortality [1]. ANGPTL4 is implicated as a pro-angiogenic factor [4], and tumorderived ANGPTL4 has been shown to promote metastasis by disrupting vascular integrity [9]. The explanation of these conflicting results and the underlying mechanism of ANGPTL4 activity in tumor cells have not been fully clarified. Recent reports demonstrate that ANGPTL4 expression is upregulated in the majority of human cancers including ESCC [6, 10]. To explore the precise role of ANGPTL4 in ESCC pathogenesis, we detected ANGPTL4 expression levels in tissue and serum samples from ESCC patients treated with radical resection

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