Expression of proteasome subunit beta type 4 in hepatocellular carcinoma and its association with prognosis

Objective To investigate the expression of proteasome subunit beta type 4( PSMB4) in hepatocellular carcinoma( HCC) tissue and normal liver tissue and its significance in clinical prognosis. Methods Eight fresh HCC tissue specimens were collected from the patients who underwent surgical treatment in Affiliated Hospital of Nantong University from January to October,2017,and Western Blot was used to measure the protein expression of PSMB4 in HCC tissue and the corresponding adjacent tissue. A total of 105 paraffin-embedded HCC tissue specimens and 25 paraffin-embedded normal liver tissue specimens,which were preserved in Affiliated Hospital of Nantong University from January 2009 and October 2012,were collected,and immunohistochemistry was used to measure the expression of PSMB4.According to the expression of PSMB4,105 HCC patients were divided into high PSMB4 expression group with 57 patients and low PSMB4 expression group with 48 patients. The independent samples t-test was used for comparison of continuous data between groups,and the chi-square test was used for comparison of categorical data between groups. The Cox proportional-hazards regression model and the Kaplan-Meier survival curves were used to analyze the clinicopathological features and prognosis of the patients in the two groups. Results There were significant differences between the two groups in hepatitis B virus infection,maximum tumor diameter,degree of tumor differentiation,and TNM stage( χ2= 22. 482,8. 219,14. 964,and 6. 587,all P < 0. 05). Among the 105 HCC patients,57( 54. 29%) had high PSMB4 expression and 48( 45. 71%) had low PSMB4 expression,while among the 25 normal liver tissue specimens,8( 32%) had high PSMB4 expression and 17( 68%) had low PSMB4 expression or no PSMB4 expression,and there was a significant difference in PSMB4 expression between the two groups( χ2= 4. 011,P < 0. 05). PSMB4 staining was mainly distributed in the cytoplasm and nucleus,with an appearance of brown or brownish yellow particles. Among the 8 fresh HCC tissue specimens,7 specimens had significantly higher protein expression of PSMB4 than the corresponding adjacent tissue specimens( all P < 0. 05). The patients' 5-year survival was associated with tumor size( P = 0. 01),metastasis( P < 0. 001),degree of tumor differentiation( P = 0. 01),TNM stage( P = 0,003),and PSMB4 expression( P <0. 001),among which metastasis( hazard ratio [HR]= 11. 375,95% confidence interval[CI]: 4. 911-26. 348,P < 0. 001) and high PSMB4 expression( HR = 6. 834,95% CI: 2. 939-15. 889,P < 0. 001) were independent risk factors in HCC patients. The high PSMB4 expression group had a significantly lower 5-year survival rate than the low PSMB4 expression group( 27. 6% vs 79. 2%,χ2= 22. 96,P <0. 05). Conclusion There is an increase in the expression of PSMB4 in HCC tissue,and high expression of PSMB4 is an independent risk factor for poor prognosis in HCC patients,suggesting that PSMB4 may serve as a potential prognostic marker or a potential target for treatment.