High expression of AGR2 in lung cancer is predictive of poor survival.

Mohammed Alavi,Vei Mah,Lora Bagryanova,Alvin Y Liu,Steve Horvath,Erin L Maresh,Lee Goodglick,David Chia

doi:10.1186/s12885-015-1658-2

Abstract

BackgroundAnterior gradient 2 (AGR2) is a protein disulfide isomerase-like protein widely expressed in many normal tissues as well as cancers. In our study, non-neoplastic bronchial epithelial cells as well as non-small cell lung cancer (NSCLC) cells express AGR2 protein.MethodsAGR2 expression was analyzed on lung tissue microarrays. Tumor staining was correlated with clinical outcomes.ResultsOn a lung cancer tissue microarray using immunohistochemistry, expression levels in cancer showed generally decreasing intensities in order from adenocarcinomas with mucinous components, other adenocarcinomas, squamous carcinomas, to large cell carcinomas. The study cohort was comprised of 400 cases. As a group, there was a slight trend of lower expression with increasing tumor grade. AGR2 expression level was a significant predictor of overall survival in younger patients only. Patients under 65 with lower levels showed a significantly better survival for both men and women. Patients over 65, in contrast, showed no such trend.ConclusionsNearly all NSCLC tumors show AGR2 expression. Lung cancer expression of AGR2 has prognostic value for younger patients.

Highlights

Anterior gradient 2 (AGR2) is a protein disulfide isomerase-like protein widely expressed in many normal tissues as well as cancers
Expression patterns of AGR2 Higher levels of AGR2 expression were seen in nonneoplastic bronchial epithelium compared to non-small cell lung cancer (NSCLC) cells
In all NSCLC, AGR2 expression appeared to be inversely correlated to grade (P = 0.004), the major contributor was the lower expression in grade 4 tumors

Summary

Introduction

Anterior gradient 2 (AGR2) is a protein disulfide isomerase-like protein widely expressed in many normal tissues as well as cancers. According to the American Cancer Society approximately 224,210 individuals in the United States will be diagnosed with the disease and 159,260 (71 %) will die of it in 2014 [1] Most of these are classified as non-small cell lung cancers (NSCLC), and include adenocarcinomas, squamous carcinomas, large cell carcinomas as well as less commonly occurring histopathologic patterns such as adenosquamous carcinoma. Expression of AGR2 is increased in the tumor epithelial cells; normal luminal cells have no detectable expression [3, 4]. Besides differential expression in tumor grades, AGR2 expression is found preferentially in the adenocarcinoma type than the squamous cell carcinoma type of NSCLC [9]. Oral squamous cell carcinoma has recently been reported to express AGR2 [11]

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