OncoTargets and Therapy (Feb 2018)
Low levels of tumor suppressor candidate 3 predict poor prognosis of patients with hepatocellular carcinoma
Abstract
Xu-Ren Sheng,1,2,* Song-Ge Xing,2,3,* Run-Dong Wang,2 Kang Chen,2 Wei-Dong Jia1,2 1Department of Liver Surgery, Affiliated Provincial Hospital, Anhui Medical University, 2Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, 3CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, People’s Republic of China *These authors contributed equally to this work Purpose: The tumor suppressor candidate 3 (TUSC3) has been considered to be closely associated with the occurrence, development and invasion of various malignant tumors. However, the expression of TUSC3 in hepatocellular carcinoma (HCC) tissues remains ambiguous. The purpose of this research was to investigate the expression of TUSC3 in HCC tissues and analyze the relationship between TUSC3 levels and clinicopathological characteristics and prognosis of HCC patients. Materials and methods: Immunohistochemistry was used to detect the expression of TUSC3 in HCC and the corresponding para-cancerous tissues from 92 samples of HCC patients. mRNA and protein expression levels of TUSC3 were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays in 25 paired HCC and corresponding adjacent nontumor tissues. Furthermore, statistical analysis was applied to evaluate the correlation between TUSC3 level and the clinicopathological features and prognosis of HCC patients. Results: Immunohistochemical assay indicated that the expression of TUSC3 was significantly lower in HCC tissues when compared with the corresponding para-cancerous tissues (χ2=11.512, P=0.001). The analysis of clinicopathological characteristics showed that low expression of TUSC3 in HCC tissues was significantly associated with Edmondson grade, Barcelona Clinic Liver Cancer stage and tumor size (P=0.008, 0.009 and 0.020, respectively). Univariate analysis showed that the expression of TUSC3 was strongly correlated with overall survival (OS) and disease-free survival (DFS) after radical surgery in HCC patients (P<0.001, P<0.001, respectively). Multivariate analysis revealed that the TUSC3 level was an independent risk factor for OS and DFS in HCC patients (P=0.001, P<0.001, respectively). Results of qRT-PCR and Western blot assays indicated that the level of TUSC3 in HCC tissues was significantly lower than that in the corresponding adjacent noncancerous tissues (P<0.01, P<0.001). Conclusion: The expression of TUSC3 in HCC was significantly downregulated and was correlated with tumor progression and prognosis, which could be used as an independent predictor of prognosis in HCC patients. Keywords: TUSC3, hepatocellular carcinoma, prognosis, immunohistochemistry, overall survival
