High expression of IMPDH2 is associated with aggressive features and poor prognosis of primary nasopharyngeal carcinoma

Yi Xu,Huiwen Weng,Ying Gao,Jian Rong,Miao Yun,Zhousan Zheng,Kebing Wang,Jiaxing Zhang,Cui Chen,Shiyu Duan,Sheng Ye

doi:10.1038/s41598-017-00887-1

Abstract

Inosine monophosphate dehydrogenase type II (IMPDH2) has been shown to play critical roles in the development and progression of several human cancers. However, little is known about IMPDH2 expression and its clinical significance in nasopharyngeal carcinoma (NPC). Western blotting, qRT-PCR and immunohistochemistry were employed to evaluate IMPDH2 expression in NPC cell lines and tissues. In our study, elevated expression of IMPDH2 was observed at both the protein and mRNA levels in NPC cell lines than in NPEC2 Bmi-1. IMPDH2 protein expression was markedly higher in NPC tissues than in adjacent non-tumorous tissues. Moreover, IMPDH2 expression in NPC correlated with several clinicopathological parameters, including T classification (P = 0.023), TNM stage (P = 0.020), distant metastasis (P = 0.001) and death (P = 0.002). Further Cox regression analysis suggested that IMPDH2 expression was an independent prognostic factor for overall survival (P = 0.001) and disease-free survival (P < 0.001). In addition, stratified survival analysis showed that high expression of IMPDH2 could be a prognostic factor for NPC patients with TNM stage I/II (OS: P = 0.012; DMFS: P = 0.007), TNM stage III/IV (OS: P = 0.028; DMFS: P = 0.020). Our study demonstrates IMPDH2 may be served as an independent prognostic biomarker for NPC patients, in which high IMPDH expression suggests poor prognosis of NPC patients.

Highlights

Nasopharyngeal carcinoma (NPC) is one of the most prevalent human head and neck malignancies in Southern China, Southeast Asia and North Africa[1,2,3]
To our knowledge, the C666 cell line was the only native EBV-infected nasopharyngeal carcinoma (NPC) cell line among these NPC cell lines. These results suggest that high expression of IMPDH1 in C666 may be associated with EBV-infected NPC cell line
Our results revealed that high expression of IMPDH2 could be a prognostic factor for NPC patients with TNM stage I/II (OS: P = 0.012, Fig. 5C; Distant metastasis-free survival (DMFS): P = 0.007, Fig. 5D), TNM stage III/IV (OS: P = 0.028, Fig. 5E; DMFS: P = 0.020, Fig. 5F)

Summary

Introduction

Nasopharyngeal carcinoma (NPC) is one of the most prevalent human head and neck malignancies in Southern China, Southeast Asia and North Africa[1,2,3]. Previous studies have demonstrated that IMPDH was associated with cell growth, malignant transformation and differentiation[8,9,10]. In mammalian species, it has two ubiquitously expressed isoforms, IMPDH1 and IMPDH2, which are encoded by distinct genes with 85% of their amino acid sequence conserved[11]. The protein expression level of IMPDH2 was found to be significantly upregulated in prostate, kidney and bladder cancers and could be a potential biomarker for these diseases[2, 17]. Immunohistochemistry (IHC) was utilized to examine the expression level of IMPDH2 in NPC tissues and adjacent normal nasopharyngeal tissues. The relationship between IMPDH2 expression and various clinicopathologic parameters was evaluated to investigate the prognostic impacts of IMPDH2 in NPC patients

Methods

Results

Conclusion