Decreased Expression of Beclin 1 Correlates Closely with Bcl-xL Expression and Poor Prognosis of Ovarian Carcinoma

Huan-Xin Lin,Dan Xie,Guo-Fen Yang,Hui-Juan Qiu,Yi-Xin Zeng,Mu-Yan Cai,Hsiang-Fu Kung,Hui-Lan Rao,Fei Zeng,Xiao-Feng Zhu,Xin-Yuan Guan

doi:10.1371/journal.pone.0060516

Abstract

BackgroundIt has been suggested that autophagy-related Beclin 1 plays a critical role in the regulation of tumor development and/or progression, but its prognostic significance and relationship with Bcl-xL expression in ovarian carcinoma are unclear.Methodology/Principal FindingsIn the present study, the methods of Western blotting and immunohistochemistry (IHC) were utilized to investigate the expression status of Beclin 1 and Bcl-xL in fresh ovarian tissues and paraffin-embedded epithelial ovarian tumor tissues. Decreased expression of Beclin 1 was examined by IHC in 8.3% of normal ovaries, in 15.4% of cystadenomas, in 20.0% of borderline tumors, and in 55.6% of ovarian carcinomas, respectively. In ovarian carcinomas, decreased expression of Beclin 1 was correlated closely with ascending histological grade, later pT/pN/pM status and/or advanced clinical stage (P<0.05). In univariate survival analysis, a highly significant association between low-expressed Beclin 1 and shortened patient survival was evaluated in ovarian carcinoma patients (P<0.01), and Beclin 1 expression was an independent prognostic factor as evidenced by multivariate analysis (P = 0.013). In addition, decreased expression of Beclin 1 was inversely correlated with altered expression of Bcl-xL in ovarian carcinoma cohort, and combined analysis further showed that the low Beclin 1/high Bcl-xL group had the lowest survival rate.Conclusions/SignificanceOur findings suggest that Beclin 1 expression, as examined by IHC, could be served as an additional tool in identifying ovarian carcinoma patients at risk of tumor progression, and predicting patient survival in ovarian carcinomas with increased expression of Bcl-xL.

Highlights

Ovarian cancer is the most common cause of cancer death among gynecological malignancies worldwide, and the incidence has been steadily increasing in Asian countries such as China and Singapore [1,2]
We report that decreased expression of Beclin 1 is closely associated with a more aggressive phenotype and/or poor prognosis of ovarian carcinoma synergized with increased expression of Bcl-xL
The protein expression of Beclin 1 was first examined by Western blotting in 5 pairs of primary ovarian carcinoma and adjacent normal ovarian tissues

Summary

Introduction

Ovarian cancer is the most common cause of cancer death among gynecological malignancies worldwide, and the incidence has been steadily increasing in Asian countries such as China and Singapore [1,2]. The majority of patients with ovarian carcinoma were diagnosed at advanced stages due to absence of specific symptoms and lack of reliable methods for the early detection [3]. The long-term prognosis of patients with ovarian carcinoma remains poor despite recent progress in surgical techniques and chemotherapeutic treatments [4]. More and more advances have been made in understanding the genetic alterations and biological processes in ovarian carcinoma [5]. The search for specific molecular and/or genetic alterations in ovarian carcinoma that have clinicopathologic/prognostic significance is substantially limited. It has been suggested that autophagy-related Beclin 1 plays a critical role in the regulation of tumor development and/or progression, but its prognostic significance and relationship with Bcl-xL expression in ovarian carcinoma are unclear

Methods

Results

Conclusion