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

Abstract

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 overal...

Clustering analysis and prognostic model based on PI3K/AKT-related genes in pancreatic cancer

“…Further studies have found that PPP2R3A gene overexpression promotes HK1 levels and glycolysis, thereby promoting the proliferation, invasion and migration of hepatocellular carcinoma (45). Additionally, PPP2R3 expression is associated with poor prognosis after liver transplantation in hepatocellular carcinoma patients (46). However, the role of PPP2R3A in pancreatic cancer is unclear.…”

Hypercontractile cardiac phenotype in mice overexpressing the regulatory subunit PR72 of protein phosphatase 2A

“…The promoting effects of PR72 on proliferation can also be observed in recent tumor biology studies. For instance, high expression of the PPP2R3A gene was found to be directly linked to the outcome of patients with hepatocellular carcinoma ( 37 ), which correlates with promotion of glycolysis via regulation of hexokinase 1 ( 38 ). Conversely, silencing of the PPP2R3A gene abolished glycolysis as well as proliferation, migration, and invasion in liver tumor cells.…”

“…However, recent advances in our approach to studying these subunits have revealed that posttranslational processes can impact not only the activity, but also the intracellular targeting and substrate specificity of the PP2A heterotrimer. Thus far, this has been demonstrated mainly for subunits belonging to the B and B' families (34)(35)(36). While early basic biochemical experiments have shown that PR72, a member of the B'' gene family, plays a role in regulating PP2A activity in response to varying Ca 2+ concentrations (8,9), comprehensive functional findings in both healthy and diseased hearts are still lacking.…”

The protein phosphatase-2A subunit PR130 is linked to cytotoxic protein aggregate formation in mesenchymal pancreatic ductal adenocarcinoma cells

“…These include the B-type subunits PPP2R2D in gastric cancer and PR130 (encoded by the gene PPP2R3A) in liver cancer. [22][23][24][25][26] A recent work analyzed Cancer-Genome-Atlas (TCGA) datasets and surgically removed human PDACs for a link between the PPP2R3A mRNA expression and PR130 with patient survival. PR130 was found to be associated with poor prognosis and with tumor recurrence.…”