Frequent loss expression of dab2 and promotor hypermethylation in human cancers: a meta-analysis and systematic review.

Ziyin Zhang,Xuemei Xie,Jianjian Tang,Yihua Chen

doi:10.12669/pjms.302.4486

Abstract

Objective : Disabled-2 (Dab2) is an important endocytic adaptor which plays an inhibition role in cancer cell growth. The objective of this study was to systematically review expressions of Dab2 in human cancers. Methods : Eligible studies about Dab2 in human cancers were retrieved from databases of PubMed, Embase, Web of Science. Odds Ratios (ORs) with 95% confidence intervals (CIs) were calculated using Review Manager 5.0 software and statistical analyses were performed by the SPSS 13.0 software. Results : Fourteen case-control studies with a total of 689 human tumor tissues, 332 control tissues and 32 cancer cell lines were included in the meta-analysis study. The results indicated loss expressions of Dab2 were observed in 74.9% and 46.9% in human malignant cancer tissues and cancer cell lines, respectively. The ratio of Dab2 promotor hypermethylation is 34.54% in cancer tissues which Dab2 expression are lost, but none in the control tissues or cells by Methylation-specific PCR (MSP). Conclusions : The expressions of Dab2 are frequently lost in human malignant cancer tissues, and promotor hypermethylation of Dab2 are common in human malignant cancer tissues, which is an important factor for the loss expression of Dab2 in human cancers tissues.

Highlights

The gene Disabled-2 (Dab2) which names DOC-2 (Differentially expressed in the Ovarian Carcinoma 2, DOC-2) owns two different splicing formats, and encodes two isoforms
Frequent loss expression of Dab2 was observed in various human cancers tissues: The immunostained percentage of Dab2 expression were detected in five different kinds of human cancer tissues
Some studies demonstrated that Dab2 protein was un-detectable in 70% ~ 90% human malignant cancers, including nasopharyngeal carcinomas, breast cancers, 436 Pak J Med Sci 2014 Vol 30 No 2 www.pjms.com.pk and gestational choriocarcinomas

Summary

Introduction

The gene Disabled-2 (Dab2) which names DOC-2 (Differentially expressed in the Ovarian Carcinoma 2, DOC-2) owns two different splicing formats, and encodes two isoforms Xuemei Xie, 1, 3: Department of Neurosurgery, Meishan City People’s Hospital, Meishan, Sichuan Province, 620010, China. 2, 4: Department of Pathology, People’s Liberation Army General Hospital of Chengdu Military Region, Chengdu, Sichuan Province, 610083, China. The main functional domain is the phosphotyrosine binding domain (PTB) of the N-terminal, which is a highly conserved sequence and plays a variety of functional roles in endocytosis, cell mitosis, and growth factor signaling.. The p96-Dab is essential for the development of visceral endoderm during mouse embryogenesis and homologous with 93% full-length of mouse Dab2.5-7 Mechanistically, Dab is shown to bind with the growth factor receptor binding protein 2 (Grb2), uncouple the activation of c-Fos expression and Ras/mitogen activated protein kinase (MAPK). Correspondence: October 15, 2013 November 27, 2013 December 25, 2013 and p67-Dab2). The main functional domain is the phosphotyrosine binding domain (PTB) of the N-terminal, which is a highly conserved sequence and plays a variety of functional roles in endocytosis, cell mitosis, and growth factor signaling. Especially, the p96-Dab is essential for the development of visceral endoderm during mouse embryogenesis and homologous with 93% full-length of mouse Dab2.5-7 Mechanistically, Dab is shown to bind with the growth factor receptor binding protein 2 (Grb2), uncouple the activation of c-Fos expression and Ras/mitogen activated protein kinase (MAPK).

Methods

Results

Conclusion