The prognostic value of AGR2 expression in solid tumours: a systematic review and meta-analysis

Shao-Bo Tian,Kai-Xiong Tao,Lin Wang,Jin-Bo Gao,Zheng Wang,Xue-Liang Ding,Zhi-Bo Liu,Jia Hu,Jin-Yuan Cui,Kai-Lin Cai,Guo-Bin Wang,Ya-Nan Chu,Xiao-Ming Shuai,Ji-Liang Wang

doi:10.1038/s41598-017-15757-z

Shao-Bo Tian, Kai-Xiong Tao + Show 12 more

Open Access

https://doi.org/10.1038/s41598-017-15757-z

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Abstract

The prognostic value of anterior gradient-2 (AGR2) in tumours remains inconclusive. Here, we systematically reviewed the literature evidence and assessed the association between AGR2 expression and prognosis in solid tumours. The primary outcomes were overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS)/recurrence-free survival (RFS)/progression-free survival (PFS). All analyses were performed by STATA 12.0, with the hazard ratio (HR) or odds ratios (OR), and 95% confidence interval (CI) as the effect size estimate. A total of 20 studies containing 3285 cases were included. Pooled analyses revealed that AGR2 overexpression had an unfavourable impact on OS (HR 1.93, 95% CI 1.32–2.81) and time to tumour progression (TTP) (DFS/RFS/PFS) (HR 1.60 95% CI 1.06–2.40) in solid tumour patients. Subgroup analyses indicated that AGR2 overexpression in breast cancer patients was significantly associated with poor OS (HR 3.02, 95% CI 1.03–8.81) and TTP (HR 1.93, 95% CI 1.17–3.20). Excluding breast cancer, AGR2 overexpression was also found to have a significant correlation with poor OS in the remaining solid tumour patients (HR 1.51, 95% CI 1.04–2.19). Overall, AGR2 might be a potential biomarker to predict prognosis in solid tumour patients.

Highlights

The human anterior gradient-2 (AGR2), a homologue of xenopus anterior gradient-2 (XAG-2) of Xenopus laevis[1], is a member of the protein disulfide isomerase (PDI) gene family
20 studies (19 in English and 1 in Chinese) with a total number of 3285 patients were used for analysing the relationship between AGR2 expression and solid tumour patients’ prognosis
Given that disease-free survival (DFS) /recurrence-free survival (RFS) /progression-free survival (PFS) are similar outcome endpoints, we used the time to tumour progression (TTP) to represent these three survival parameters in our meta-analysis[33]

Summary

Introduction

The human anterior gradient-2 (AGR2), a homologue of xenopus anterior gradient-2 (XAG-2) of Xenopus laevis[1], is a member of the protein disulfide isomerase (PDI) gene family. AGR2 protein weighs 19 kDa containing a short N-terminal signal peptide and a C-terminal endoplasmic reticulum retention sequence (KTEL)[2]. AGR2, physiologically localized in endoplasmic reticulum (ER), has emerged as a critical modulator of ER homeostasis[3,4]. Since AGR2 was found to be as a pro-oncogenic protein that attenuates p53 activity in 20046, AGR2’s molecular role and its clinical relevance have been increasingly investigated in cancers, including breast[7,8], lung[9], ovarian[10], prostate[11], pancreatic cancer[12], and colorectal carcinomas[13]. In other types of cancer, such as prostate cancer, ovarian cancer and colorectal cancer, the prognostic value of AGR2 remains largely inconclusive[17,18,19]. Aiming to explore the prognostic value of AGR2 in these solid tumours, we conducted this comprehensive meta-analysis

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