The clinicopathological significance and potential drug target of E-cadherin in NSCLC

• Published in: Tumor biology 2015-08, Vol.36 (8), p.6139-6148
• Main Authors: Zhong, Kaize, Chen, Weiwen, Xiao, Ning, Zhao, Jian
• Format: Article
• Language: English
• Subjects: Biomarkers, Tumor - genetics; Biomedical and Life Sciences; Biomedicine; Cadherins - genetics; Cancer Research; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Cell adhesion & migration; DNA methylation; DNA Methylation - genetics; Humans; Lung cancer; Meta-analysis; Molecular Targeted Therapy; Promoter Regions, Genetic; Protein expression; Research Article
• ISSN: 1010-4283; 1423-0380
• DOI: 10.1007/s13277-015-3298-1

Human epithelial cadherin (E-cadherin), a member of transmembrane glycoprotein family, encoded by the E-cadherin gene, plays a key role in cell-cell adhesion, adherent junction in normal epithelial tissues, contributing to tissue differentiation and homeostasis. Although previous studies indicated that inactivation of the E-cadherin is mainly induced by hypermethylation of E-cadherin gene, evidence concerning E-cadherin hypermethylation in the carcinogenesis and development of non-small cell lung carcinoma (NSCLC) remains controversial. In this study, we conducted a meta-analysis to quantitatively evaluate the effects of E-cadherin hypermethylation on the incidence and clinicopathological characteristics of NSCLC. A comprehensive search of PubMed and Embase databases was performed up to October 2014. Analyses of pooled data were performed. Odds ratios (ORs) were calculated and summarized. Our meta-analysis combining 18 published articles demonstrated that the hypermethylation frequencies in NSCLC were significantly higher than those in normal control tissues, OR = 3.55, 95 % confidence interval (CI) = 1.98–6.36, p <  0.0001. Further analysis showed that E-cadherin hypermethylation was not strongly associated with the sex or smoking status in NSCLC patients. In addition, E-cadherin hypermethylation was also not strongly associated with pathological types, differentiated status, clinical stages, or metastatic status in NSCLC patients. The results from the current study indicate that the hypermethylation frequency of E-cadherin in NSCLC is strongly associated with NSCLC incidence and it may be an early event in carcinogenesis of NSCLC. We also discussed the potential value of E-cadherin as a drug target that may bring new direction and hope for cancer treatment through gene-targeted therapy.