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Abstract
This study aims to identify novel biomarkers and therapeutic targets for lung cancer. 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. 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 = 0.0014) and multivariate analysis confirmed it to be an independent prognostic factor (P = 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. EBI3 is a potential serum and tissue biomarker as well as therapeutic target for lung cancer.
Highlights
Lung cancer is the leading cause of cancer deaths in the world [1]
Serum levels of Epstein-Barr virus–induced gene 3 (EBI3) in the training set were found to be significantly higher in lung cancer patients than in healthy volunteers; this result was observed in the validation set
EBI3 expression in lung cancers and normal tissues To screen novel molecule targets that can be used for detection of cancer at an early stage and for development of novel treatment strategies, we first carried out genome-wide gene expression profile analysis of 120 lung carcinomas, using a cDNA microarray [6,7,8,9,10]
Summary
The overall 5-year survival rate of patients with non–small cell lung cancer (NSCLC) is only 10% to 15%, that of patients with stage IA NSCLC exceeds 80% [2]. Antigen (CEA), serum cytokeratin 19 fragment (CYFRA211), and progastrin-releasing peptide (Pro-GRP) are clinically available for lung cancer diagnosis. These markers are not entirely useful for screening early-stage cancers because of their relatively low sensitivity and specificity [3, 4].
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