Prognostic and Clinicopathological Significance of X-Box-Binding Protein 1 and N-Acetyltransferase 1 in Gallbladder Cancer.

Rushi Liu,Daiqiang Li,Xiongying Miao,Qiong Zou,Zhengchun Wu,Zhulin Yang,Yuanfang Zhang,Yuan Yuan

doi:10.3389/fonc.2020.01124

Abstract

Background: X-box-binding protein 1 (XBP1) and N-acetyltransferase 1 (NAT1) are involved in oncogenesis and progression of many human cancer types. However, the roles of XBP1 and NAT1 in gallbladder cancer (GBC) are never reported.Methods: We examined XBP1 and NAT1 expression in GBC and matched adjacent non-tumor tissues via Western blotting. Then, we assayed XBP1 and NAT1 expression in 215 GBCs, including 69 squamous cell/adenosquamous carcinomas (SC/ASCs) and 146 adenocarcinomas (ACs) with immunohistochemistry. Their prognostic and clinicopathological significance was further evaluated using the χ2 test or Fisher's exact test, Kaplan–Meier univariate survival analysis, and log-rank tests.Results: XBP1 expression was upregulated, and NAT1 expression was downregulated in GBC. Immunohistochemical results showed that XBP1 expression was negatively associated with NAT1 expression in GBC, including SC/ASC and AC. The rate of patients with an age of more than 45 years, positivity of lymph node metastasis, and invasion were significantly higher in SC/ASC than those in AC (all P < 0.05). The percentage of XBP1-positive and NAT1-negative expression was significantly higher in the cases with poor differentiation, advanced tumor, nodes, and metastases (TNM) stage, lymph node metastasis, invasion, and only receiving biopsy in GBC, SC/ASC, and AC (all P < 0.05). XBP1-positive and NAT1-negative expression was positively related to larger tumor size (>3 cm) in GBC and AC. There was a negative association between XBP1 and NAT1 expression in GBC, SC/ASC, and AC (all P < 0.05). Positive XBP1 and negative NAT1 expression was closely associated with decreased overall survival in GBC, SC/ASC, and AC patients (all P < 0.05). The multivariate Cox regression analysis showed that positive XBP1 or negative NAT1 expression was an independent factor for poor prognosis in gallbladder SC/ASC and AC patients.Conclusions: This study indicates that positive XBP1 and negative NAT1 expression are closely associated with the clinicopathological and biological behaviors and poor prognosis in GBC.

Highlights

Gallbladder cancer (GBC), the most common biliary malignant tumor, is an extremely fatal disease with poor prognosis
Our results showed that lymph node metastasis and invasion occur in SC/ASC compared with those in AC
We found that other clinicopathological features, including tumor differentiated degree, tumor size, the occurrence of gallstone, TNM stages, and X-box-binding protein 1 (XBP1) and N-acetyltransferase 1 (NAT1) expression were non-significantly different in SC/ASC and AC

Summary

Introduction

Gallbladder cancer (GBC), the most common biliary malignant tumor, is an extremely fatal disease with poor prognosis. Due to commonly presenting asymptomatic in early stage, GBC patients are often difficult to be diagnosed at this stage [5, 6]. When symptoms such as jaundice and pain occur, patients are mostly in the late stage, with invasion and metastasis, and miss the opportunity to receive radical surgery [6]. Postoperative adjuvant therapies cannot significantly improve the prognosis of GBC patients [7]. The roles of XBP1 and NAT1 in gallbladder cancer (GBC) are never reported

Methods

Results

Conclusion