Low expression of organic anion-transporting polypeptide 1B3 predicts a poor prognosis in hepatocellular carcinoma

Shihan Chen,Qingsong Deng,Ling Shuai,Chang Zhang,Yuelong Chai,Leida Zhang,Xiaofei Wang,Kun Li,Jiayun Jiang,Kai Feng,Kuansheng Ma

doi:10.1186/s12957-020-01891-y

Abstract

ObjectiveTo detect the expression level of organic anion-transporting polypeptide 1B3 (OATP1B3) in hepatocellular carcinoma (HCC) and to determine the relationship between OATP1B3 expression, clinicopathological features, and prognosis.MethodsImmunohistochemical (IHC) staining was performed to detect the expression of OATP1B3 in 131 HCC specimens and in 89 adjacent nontumorous tissues. Moreover, the expression levels of OATP1B3 in 30 pairs of tumor and matched adjacent nontumorous tissues were detected by quantitative real-time polymerase chain reaction, and 34 pairs of tumor and matched adjacent nontumorous tissues were detected by Western blotting. The χ2 test was applied to analyze the correlation between OATP1B3 expression and the clinical parameters of HCC patients. The prognostic value of OATP1B3 in HCC patients was estimated by Kaplan-Meier survival analysis and the Cox stepwise proportional hazards model.ResultsCompared with that in adjacent nontumorous tissues (25.8%, 23/89), OATP1B3 expression was significantly downregulated in tumor tissues (59.5%, 78/131) (P < 0.0001). Moreover, OATP1B3 expression was markedly correlated with tumor size, recurrence, tumor differentiation, and tumor node metastasis (TNM) stage (P < 0.05 for each). However, age, sex, tumor capsule status, HBsAg, cirrhosis, tumor number, vascular invasion, and serum alpha fetoprotein were not associated with OATP1B3 expression. The overall survival (OS) and disease-free survival (DFS) of HCC patients who had high expression of OATP1B3 were significantly longer than those of patients with low expression (33.0% vs 12.9%, P = 0.001; 18.8% vs 5.3%, P < 0.0001). Cox multivariate analysis showed that OATP1B3, invasion, and TNM stage (P < 0.05 for each) were independent prognostic factors of OS in HCC patients and that OATP1B3 and TNM stage (both P < 0.05) were independent prognostic factors of DFS in HCC patients.ConclusionsThe expression of OATP1B3 in HCC patients was significantly lower than that in adjacent nontumorous tissues. OATP1B3 expression may be a potential prognostic marker in HCC patients.

Highlights

Liver cancer is one of the most common alimentary system malignancies and has high morbidity and mortality rates
Expression of organic anion-transporting polypeptide 1B3 (OATP1B3) in Hepatocellular carcinoma (HCC) samples The expression level of OATP1B3 in HCC cancer tissue samples was evaluated according to the aforementioned semiquantitative IHC scoring method
We found that the OATP1B3 protein was localized to both the plasma membrane and the cytoplasm in tumor tissue samples

Summary

Introduction

Liver cancer is one of the most common alimentary system malignancies and has high morbidity and mortality rates. HCC is often diagnosed at an advanced stage, as early symptoms are inconspicuous. It seriously endangers human health and life. Some progress has been made in understanding the epidemiology, pathogenesis, diagnosis, and treatment of HCC in recent years [4], its high recurrence and metastasis rates still seriously affect patient survival. The prognosis of HCC patients estimated by the Barcelona Clinic Liver Cancer (BCLC) and Tumor Node Metastasis (TNM) staging classification systems is often inaccurate [5]. This may arise because the tumor malignant phenotype is not included in these classification systems.

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Conclusion