Decreased expression of Sushi Domain Containing 2 correlates to progressive features in patients with hepatocellular carcinoma.

Xin-Rui Liu,You-Qin Xu,Li-Min Luo,Cui-Xia Cai,Rong Shi,Jun Zeng,Wen-Ling Zheng,Min Wei,Wen-Li Ma

doi:10.1186/s12935-016-0286-5

Xin-Rui Liu, You-Qin Xu + Show 7 more

Open Access

https://doi.org/10.1186/s12935-016-0286-5

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Abstract

BackgroundSushi Domain Containing 2 (SUSD2) has been identified as a regulator of colon and breast cancer. Increasing evidence suggests that SUSD2 plays a key role in tumorigenesis. However, the SUSD2 expression status and its functions in hepatocellular carcinoma (HCC) are still unrevealed. In the present study, we intended to investigate SUSD2 expression status and its correlation with the clinicopathological features in HCC patients. Furthermore,we examined the influence of SUSD2 on the proliferation, apoptosis, invasion and migration of the HCC cell lines HepG2 and SMMC7721.MethodsWe evaluated the SUSD2 expression in HCC tissues and paired normal liver tissues by quantitative real-time PCR and western blotting analysis. The clinicopathological significance of SUSD2 was investigated by immunohistochemistry (IHC) on a HCC tissue microarray. Receiver operating characteristic (ROC) analysis was applied to determine the optimal cut-off score for positive expression of SUSD2. The correlation between SUSD2 protein expression and clinicopathological features of HCC was analyzed by Chi square test. The cell proliferation, apoptosis, invasion and migration potential were observed to detect the functions of SUSD2 in HCC cells.ResultsDecreased expression of SUSD2 mRNA and protein were observed in the majority of HCC tissues, compared with paired normal liver tissues. When SUSD2 high expression percentage was determined to be above 52.5 % (area under ROC curve = 0.769, P = 0.000), low expression of SUSD2 was observed in 62.2 % (112/180) of HCC tissues and high expression of SUSD2 was observed in all normal liver tissues (16/16) by IHC. Decreased expression of SUSD2 in patients was correlated with high histological grade (χ2 = 5.198, P = 0.023), advanced clinical stage (χ2 = 30.244, P = 0.000), pT status (χ2 = 33.175, P = 0.000), pN status (χ2 = 4.785, P = 0.029), pM status (χ2 = 4.620, P = 0.032). Down-regulation of SUSD2 promoted cell proliferation,invasion and migration,reduced the cell apoptosis.ConclusionsOur findings suggest that SUSD2 may play as a tumor suppressor in HCC cells and could be served as an additional potential marker for diagnosis.

Highlights

Sushi Domain Containing 2 (SUSD2) has been identified as a regulator of colon and breast cancer
These results show that exogenous overexpression of SUSD2 suppresses the cell proliferation, invasion and migration of hepatocellular carcinoma (HCC) cells and promotes the cell apoptosis in vitro
Western blotting showed that 7/8 HCCs displayed reduced level of SUSD2 compared with the adjacent normal liver tissues (Fig. 1a)

Summary

Introduction

Sushi Domain Containing 2 (SUSD2) has been identified as a regulator of colon and breast cancer. The SUSD2 expression status and its functions in hepatocellular carcinoma (HCC) are still unrevealed. We intended to investigate SUSD2 expression status and its correlation with the clinicopathological features in HCC patients. We examined the influence of SUSD2 on the proliferation, apoptosis, invasion and migration of the HCC cell lines HepG2 and SMMC7721. Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide. Liu et al Cancer Cell Int (2016) 16:15 with HCC is only 7 % [3]. Molecular analysis of HCC revealed genetic and epigenetic alterations that lead to the deregulation of key proto-oncogenes and tumor suppressor genes including P53, β-catenin, ErbB receptor factor, p16, E-cadherin, and cyclooxygenase 2 in this cancer [6, 7]. It is prevalent to discovery novel biomarkers for accurate diagnosis, prognosis and individualized medication of HCC

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