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

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

doi:10.3389/fonc.2020.01124

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

Front Oncol. 2020 Jul 24:10:1124. doi: 10.3389/fonc.2020.01124. eCollection 2020.

Authors

Rushi Liu¹, Zhengchun Wu², Yuanfang Zhang¹, Xiongying Miao², Qiong Zou³, Yuan Yuan³, Daiqiang Li⁴, Zhulin Yang²

Affiliations

¹ Department of Medical Laboratory, Immunodiagnostic Reagents Engineering Research Center of Hunan Province, School of Medicine, Hunan Normal University, Changsha, China.
² Hunan Provincial Key Laboratory of Hepatobiliary Disease Research, Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, China.
³ Department of Pathology, Third Xiangya Hospital, Central South University, Changsha, China.
⁴ Department of Pathology, Second Xiangya Hospital, Central South University, Changsha, China.

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.

Keywords: N-acetyltransferase 1; X-box-binding protein 1; clinicopathological significance; gallbladder cancer; prognosis.