Identification of Epstein-Barr Virus–Induced Gene 3 as a Novel Serum and Tissue Biomarker and a Therapeutic Target for Lung Cancer

Abstract

Purpose: This study aims to identify novel biomarkers and therapeutic targets for lung cancer. Experimental Design: We carried out gene expression profile analysis of 120 lung cancers to screen for genes encoding transmembrane/secretory molecules that are commonly transactivated in lung cancers. Epstein-Barr virus-induced gene 3 (EBI3), which encodes a secretory glycoprotein, was selected as a good candidate. Immunohistochemical staining using tissue microarray consisting of 414 non-small cell lung cancers was applied to examine the expression level and prognostic value of EBI3. Serum EBI3 levels in 400 individuals for training assays (274 lung cancers and 126 healthy volunteers) and those in 173 individuals for validation analysis (132 lung cancers and 41 healthy volunteers) were measured by ELISA. The role of EBI3 in cancer cell growth was examined by siRNA and cell growth assays, using cells stably expressing exogenous EBI3.Results: Immunohistochemical staining of EBI3 using tissue microarrays revealed that a high level of EBI3 expression was associated with a poor prognosis of lung cancer (P ¼ 0.0014) and multivariate analysis confirmed it to be an independent prognostic factor (P ¼ 0.0439). Serum levels of EBI3 in the training set were found to be significantly higher in lung cancer patients than in healthy volunteers; this result was also observed in the validation set. Furthermore, reduction in EBI3 expression by siRNA suppressed cancer cell proliferation whereas induction of exogenous EBI3 conferred growth-promoting activity.Conclusions: EBI3 is a potential serum and tissue biomarker as well as therapeutic target for lung cancer.

Expression of Epstein-Barr virus-induced gene 3 in cervical cancer: Association with clinicopathological parameters and prognosis

“…EBI3 was also found to be highly expressed in patients with non-small cell lung cancer (10). Furthermore, strong EBI3 expression in lung cancer tissues has been revealed to be correlated with a poor patient prognosis (10).…”

“…Previously, certain studies have revealed the presence of EBI3 overexpression in a series of tumors (8)(9)(10)(11). EBI3 was also found to be highly expressed in patients with non-small cell lung cancer (10).…”

“…Previously, certain studies have demonstrated that EBI3 expression is also present in lung cancer and colorectal cancer tissues and plays important functions in the progression of these tumors (10,11). Using tissue microarrays, Nishino et al also revealed that a high level of EBI3 expression is correlated with an unfavorable poor prognosis in lung cancer patients (10).…”

“…Previously, certain studies have demonstrated that EBI3 expression is also present in lung cancer and colorectal cancer tissues and plays important functions in the progression of these tumors (10,11). Using tissue microarrays, Nishino et al also revealed that a high level of EBI3 expression is correlated with an unfavorable poor prognosis in lung cancer patients (10). Additional studies have confirmed that EBI3 expression is an independent prognostic factor for disease outcome in lung and colorectal cancer, as well as Burkitt lymphoma (10)(11)(12).…”

“…Using tissue microarrays, Nishino et al also revealed that a high level of EBI3 expression is correlated with an unfavorable poor prognosis in lung cancer patients (10). Additional studies have confirmed that EBI3 expression is an independent prognostic factor for disease outcome in lung and colorectal cancer, as well as Burkitt lymphoma (10)(11)(12). However, the clinical significance of EBI3 in cervical cancer and the potential of EBI3 as a therapeutic target for this disease have not been clarified.…”