High expression of junctional adhesion molecule-A is associated with poor survival in patients with epithelial ovarian cancer.

Bukumiric Zoran,Boljevic Ivana,Malisic Emina,Jankovic Radmila,Milovic-Kovacevic Marijana,Jovanic Irena

doi:10.1177/1724600819850178

Abstract

Aberrant expression of different tight junction proteins, including the junctional adhesion molecule-A (JAM-A), has been frequently reported in association with tumor progression of several malignancies. To our knowledge, this is the first study examining the clinical significance of JAM-A gene expression in epithelial ovarian cancer. JAM-A expression levels in 44 epithelial ovarian cancer and 12 benign formalin-fixed paraffin-embedded samples were determined by reverse transcription quantitative polymerase chain reaction. Receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic and prognostic potential of JAM-A. Associations between JAM-A expression and clinicopathological characteristics of epithelial ovarian cancer were analyzed using Fisher's exact test. The Kaplan-Meier method and univariate Cox regression analysis were used for the survival analysis. P ⩽ 0.05 was considered statistically significant. ROC curve analyses showed that JAM-A gene expression exhibits both diagnostic and prognostic performance in epithelial ovarian cancer (area under the curve (AUC) 0.640, 95% confidence interval (CI) 0.488, 0.792, sensitivity 43.18%, specificity 100% and AUC 0.621, 95% CI 0.427, 0.816, sensitivity 52.63%, specificity 85%, respectively). JAM-A expression was significantly associated with International Federation of Gynecologists and Obstetricians (FIGO) stage (P =0.049) and the Kaplan-Meier method demonstrated that patients with high expression of JAM-A had significantly worse overall survival compared to patients with low JAM-A expression (P =0.004). Moreover, univariate Cox regression analysis showed that FIGO stage, peritoneal metastasis, residual tumor and JAM-A expression were significantly associated with reduced overall survival in epithelial ovarian cancer. Our results indicate that high levels of JAM-A expression are associated with an advanced clinicopathological feature and may have diagnostic potential; also, it could be a predictor of poor overall survival in patients with epithelial ovarian cancer.

Highlights

Ovarian cancer comprises a very heterogeneous group of diseases,[1] with epithelial ovarian cancer (EOC) being the most common and aggressive type which is responsible for the majority of deaths associated with a gynecological malignancy.[2]
The Receiver operating characteristic (ROC) curve analysis used to determine the diagnostic efficiency of Junctional adhesion molecule-A (JAM-A), in terms of distinguishing between benign and malignant ovarian tumor samples, yielded a cut-off value of 1.14 with an area under the curve (AUC) of 0.640
Within the malignant ovarian tumors, we identified a junctionaladhesion molecules (JAMs)-A threshold that maximized sensitivity and specificity in predicting poor outcome with a cut-off value of 1.80 (AUC 0.621, 95% CI 0.427, 0.816, P=0.013) (Table 1) (Figure 1(a) and (b))

Summary

Introduction

Ovarian cancer comprises a very heterogeneous group of diseases,[1] with epithelial ovarian cancer (EOC) being the most common and aggressive type which is responsible for the majority of deaths associated with a gynecological malignancy.[2]. It is expressed in various cell types,[7,8] including epithelial and endothelial cells, and it is involved in the regulation of several processes, such as cell polarity,[9] platelet activation,[10] angiogenesis,[11] and leukocyte migration.[12]

Methods

Results

Conclusion