Overexpression of Pleomorphic Adenoma Gene-Like 2 Is a Novel Poor Prognostic Marker of Prostate Cancer.

Jia Guo,Min Wang,Zhishun Wang,Xiuheng Liu,Gagan Deep

doi:10.1371/journal.pone.0158667

Jia Guo, Min Wang + Show 3 more

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https://doi.org/10.1371/journal.pone.0158667

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Journal: PloS one	Publication Date: Aug 18, 2016
Citations: 15	License type: CC BY 4.0

Affiliation: Wuhan University, Renmin Hospital of Wuhan University

Abstract

Pleomorphic adenoma gene like-2 (PLAGL2) is a member of the PLAG gene family. Previous studies have revealed that overexpression of PLAGL2 is associated with many human cancers. However, it has been reported that PLAGL2 also plays as a tumor suppressor. The precise role of PLAGL2 in prostate cancer (PCa) is still unknown. The aim of this study was to investigate the expression and prognostic value of PLAGL2 in PCa. Data from microarray datasets demonstrated that the DNA copy number and mRNA level of PLAGL2 were significantly increased in PCa compared with normal prostate. qRT-PCR and western blot analysis from paired PCa samples and prostate cell lines confirmed upregulated mRNA and protein expression levels in PCa. Immunohistochemistry analysis showed that staining of PLAGL2 in PCa tissues was significantly higher than that in benign prostatic hyperplasia (BPH) tissues. In addition, the high expression of PLAGL2 was only involved in preoperative PSA, but was not related to age, Gleason score, seminal vesicle invasion, surgical margin status, clinical stage and positive lymph node metastasis. Moreover, our results showed that PLAGL2 was an independent prognostic factor for biochemical recurrence (BCR)-free survival and overall survival (OS) of PCa patients, and overexpressed PLAGL2 was related to early development of BCR and poor OS. In conclusion, our findings suggest that PLAGL2 is overexpressed in PCa. The increased expression of PLAGL2 correlates to PCa progression following radical prostatectomy and may serve as a novel poor prognostic marker for PCa.

Highlights

In the developed countries, prostate cancer (PCa) has been proved to be the second most common cancer, which has become one of the leading causes of cancer death in men [1]
The DNA copy number of Pleomorphic adenoma gene like-2 (PLAGL2) was greatly increased in PCa compared to normal prostate (Fig 1)
The results showed that the expression of PLAGL2 mRNA was significantly higher in PCa than in normal prostate (Fig 1)

Summary

Introduction

Prostate cancer (PCa) has been proved to be the second most common cancer, which has become one of the leading causes of cancer death in men [1]. More PCa patients have been diagnosed at younger ages in recent years [2]. There are already many treatment options for localized PCa, including radical prostatectomy, hormonal androgen deprivation therapy, radiotherapy, brachytherapy, and active surveillance [3]. The prognosis is good for patients with localized or regional PCa, there are cases of aggressive PCa which. In the United States, the 5-year survival rate of the patients who develop metastatic disease is only 29% [6]. There are no reliable biomarkers for prediction or effective therapies of metastatic PCa

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