J Cancer 2017; 8(16):3343-3355. doi:10.7150/jca.20739

Research Paper

The Prognostic Value of Peripheral Benzodiazepine Receptor in Patients with Esophageal Squamous Cell Carcinoma

You-Fang Chen1*, Jing-Dun Xie1*, Yu-Chuan Jiang2*, Dong-Tai Chen1, Jia-Hao Pan1, Yong-Hua Chen1, Yun-Fei Yuan3, Zhe-Sheng Wen2✉, Wei-An Zeng1✉

1. Department of Anesthesiology, Cancer Center, Sun Yat-Sen University, State Key Laboratory of Oncology in South China, Guangzhou510060, Guangdong, China;
2. Department of Thoracic Oncology, Cancer Center, Sun Yat-Sen University, State Key Laboratory of Oncology in South China, Guangzhou510060, Guangdong, China;
3. Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-Sen University, State Key Laboratory of Oncology in South China, Guangzhou510060, Guangdong, China.
* These authors contributed equally to this work.

Abstract

Background: The peripheral benzodiazepine receptor (PBR) has previously been reported as an oncogene in prostate, breast and colorectal cancers, but its prognostic value, biological behavior and function in esophageal squamous cell carcinoma (ESCC) has not been investigated.

Methods: qRT-PCR, western blotting and immunohistochemistry (IHC) were used to detect PBR expression in ESCC and matched non-cancerous tissues. Based on all of the significantly independent factors, a nomogram was established to predict the prognosis of ESCC patients. In addition, we performed comprehensive in vitro experiments to study the functions of PBR in cell growth, colony formation, and migration ability, as well as its relationship with epithelial-mesenchymal transition (EMT) related proteins in ESCC cells.

Results: The mRNA and protein expression levels of PBR in ESCC were higher than those in adjacent non-tumor esophageal epithelial tissues. The IHC results demonstrated that PBR expression was an independent prognostic factor in ESCC survival, patients with higher PBR expression had a poorer survival than those with low expression, and PBR expression was significantly associated with lymphoid nodal status. Furthermore, a nomogram was established to reliably predict the probability of death in ESCC patients, with a Harrell's c-index of 0.696. In the vitro experiments, knocking down the expression of PBR inhibited proliferation, colony formation and migration of ESCC cells, and regulated EMT-associated proteins (up-regulation of E-cadherin, ZO-1 and β-catenin and concomitant with down-regulation of Fibronectin and N-cadherin).

Conclusions: PBR is an independent prognostic factor in ESCC, and it promotes ESCC progression and metastasis. Basing on PBR expression level, a nomogram is established and performs a well in predicting survival of ESCC patients.

Keywords: Peripheral benzodiazepine receptor (PBR), Esophageal squamous cell carcinoma (ESCC), Prognosis, Nomogram.

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How to cite this article:
Chen YF, Xie JD, Jiang YC, Chen DT, Pan JH, Chen YH, Yuan YF, Wen ZS, Zeng WA. The Prognostic Value of Peripheral Benzodiazepine Receptor in Patients with Esophageal Squamous Cell Carcinoma. J Cancer 2017; 8(16):3343-3355. doi:10.7150/jca.20739. Available from http://www.jcancer.org/v08p3343.htm