High nuclear ABCG1 expression is a poor predictor for hepatocellular carcinoma patient survival

Bin Xi; Fang-Zhou Luo; Bin He; Fang Wang; Ze-Kuan Li; Ming-Chun Lai; Shu-Sen Zheng

doi:10.1016/j.hbpd.2022.06.009

High nuclear ABCG1 expression is a poor predictor for hepatocellular carcinoma patient survival

Hepatobiliary Pancreat Dis Int. 2022 Aug;21(4):370-377. doi: 10.1016/j.hbpd.2022.06.009. Epub 2022 Jun 23.

Authors

Bin Xi¹, Fang-Zhou Luo¹, Bin He¹, Fang Wang², Ze-Kuan Li¹, Ming-Chun Lai¹, Shu-Sen Zheng³

Affiliations

¹ Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
² Department of Radiotherapy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China.
³ Division of Hepatobiliary and Pancreatic Surgery, Department of Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China; Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, Zhejiang University, Hangzhou 310003, China. Electronic address: shusenzheng@zju.edu.cn.

PMID: 35778316
DOI: 10.1016/j.hbpd.2022.06.009

Abstract

Background: ATP-binding cassette transporter G1 (ABCG1) regulates cellular cholesterol homeostasis and plays a significant role in tumor immunity. But, for hepatocellular carcinoma (HCC), the role of ABCG1 has not been investigated. Thus, the aim of this study was to evaluate the prognostic value and clinicopathological significance of ABCG1 in HCC.

Methods: One hundred and four adult patients with HCC were enrolled, and ABCG1 expression in paired HCC specimens was determined by immunohistochemistry. All these patients were stratified by ABCG1 expression, Kaplan-Meier analysis was used to compare the overall survival (OS) and recurrence-free survival (RFS), and Cox regression analysis was used to determine independent predictors of tumor recurrence.

Results: Upregulation of ABCG1 was observed in HCC samples compared to matched tumor-adjacent tissues. Patients with high nuclear ABCG1 expression had lower OS and RFS (P = 0.012 and P = 0.020, respectively). High nuclear ABCG1 expression was related to larger tumor size (P = 0.004) and tumor recurrence (P = 0.027). Although ABCG1 was expressed in the cytoplasm, cytosolic expression could not predict the outcome in patients with HCC. A new stratification pattern was established based on the heterogenous ABCG1 expression pattern: high risk (High^nucleus/Low^cytosol), moderate risk (High^nucleus/High^cytosol or Low^nucleus/Low^cytosol), and low risk (Low^nucleus/High^cytosol). This ABCG1-based risk stratification could distinguish the different OS and RFS in patients with HCC. Multivariate Cox regression analysis indicated that ABCG1 high risk was an independent predictor of poor RFS (P = 0.015).

Conclusions: High nuclear ABCG1 expression indicates poor prognosis in patients with HCC. Asymmetric distribution of ABCG1 in the nucleus and cytoplasm may have an important role in tumor recurrence.

Keywords: ATP-binding cassette transporter G1; Hepatocellular carcinoma; Overall survival; Prognostic factor; Progression-free survival.

MeSH terms

ATP Binding Cassette Transporter, Subfamily G, Member 1
Adult
Biomarkers, Tumor / analysis
Carcinoma, Hepatocellular* / pathology
Humans
Kaplan-Meier Estimate
Liver Neoplasms* / pathology
Neoplasm Recurrence, Local
Prognosis

Substances

ABCG1 protein, human
ATP Binding Cassette Transporter, Subfamily G, Member 1
Biomarkers, Tumor