High expression of protein phosphatase 2 regulatory subunit B'' alpha predicts poor outcome in hepatocellular carcinoma patients after liver transplantation

BACKGROUND: Protein phosphatase 2 regulatory subunit B'' alpha (PPP2R3A) gene has been reported in other tumors, but the influence of PPP2R3A gene expression on the occurrence, development, and prognosis of hepatocellular carcinoma (HCC) remains unclear. AIM: To investigate whether the PPP2R3A gene could be used to predict tumor recurrence and survival of HCC patients after liver transplantation (LT). METHODS: Diseased liver tissues of HCC patients after LT were collected as well as their clinical data and follow-up information. The immunohistochemical method was used to detect the expression of PPP2R3A protein in the tissues of 108 patients with primary liver cancer. The χ(2) test was used to analyze the relationship between PPP2R3A protein expression levels and the clinicopathological features of tumors. The Kaplan-Meier method was used to analyze overall postoperative survival. The COX proportional hazard model was used to analyze adverse prognostic factors. RESULTS: Immunohistochemistry showed that the PPP2R3A protein was mainly expressed in the cytoplasm of HCC cells. Compared to corresponding peritumoral tissues, expression was higher in HCC tissues (P ≤ 0.001). Correlation analysis showed that high PPP2R3A expression was correlated with preoperative serum alpha-fetoprotein (AFP) levels (P = 0.003), tumor-node-metastasis-t stage (P ≤ 0.001), and envelope invasion (P = 0.001). Univariate analysis showed that overall survival (P ≤ 0.001) and recurrence-free survival (P = 0.025) of patients with high PPP2R3A expression (≥ 4 points) were poor compared to those with low expression (< 4 points). The overall survival rates or recurrence-free survival rates at 1, 2, and 3 years with high PPP2R3A expression were 73%, 38%, and 23% or 31%, 23%, and 23%, respectively. Multivariate analysis showed that high PPP2R3A expression (hazard ratio = 2.900, 95% confidence interval: 1.411–5.960, P = 0.004) was an independent survival risk factor of HCC patients after LT, and it was also an independent predictor of postoperative tumor recurrence. This study also showed in patients with AFP ≥ 400 ng/mL, the overall survival (P ≤ 0.001) and recurrence-free survival (P = 0.023) of those with high PPP2R3A expression were significantly worse compared to those with low PPP2R3A expression. When PPP2R3A expression was low, the overall survival rate (P = 0.461) or recurrence-free survival rate (P = 0.072) after LT in patients with AFP < 400 ng/mL and ≥ 400 ng/mL was not significantly difference. The 1, 2, and 3 year survival rate of patients with low PPP2R3A expression and AFP < 400 ng/mL were 98%, 80%, and 69%, respectively, while patients who met Hangzhou criteria had a post-transplant 1, 2, and 3 years overall survival rate of 89%, 66%, and 55%, respectively. CONCLUSION: High expression of PPP2R3A might be a potential marker for predicting poor prognosis of HCC after LT. Combined with serum AFP levels, PPP2R3A might enhance the accuracy of predicting HCC outcome in patients after LT and supplement the efficacy of the Hangzhou criteria.