Overexpression of Pin1 and rho signaling partners correlates with metastatic behavior and poor recurrence-free survival of hepatocellular carcinoma patients

Abstract

Background: Identification of molecular markers for early detection or prediction of metastasis is crucial for both management of HCC patient postoperative treatment and identify new therapeutic targets to inhibit HCC progression and metastasis. In the current study, we investigated the clinical correlation between Pin1, RhoA and RhoC and their association with HCC metastasis.

Methods: Using a randomized study design of primary HCC samples from 139 patients, we determined messenger RNA expression of Pin1, RhoA and RhoC and their prognostic value.

Results: Our findings demonstrated for the first time the clinical correlation of Pin1 in HCC metastasis. Pin1, RhoA and RhoC transcript levels were significantly higher in HCC specimens when compared with the paired adjacent non-tumorous liver. Pin1 overexpression was closely correlated with that of RhoA (R = 0.562, p < 0.001) and RhoC (R = 0.529, p < 0.001), and their co-overexpressions correlated with metastatic HCC (p = 0.000012) and poor recurrence-free survival of HCC patients (p < 0.00001), which showed better prognostic significance than either Pin1, RhoA or RhoC overexpression alone. Co-overexpressions of Pin1 + RhoA/RhoC were also an independent factor for predicting development of metastasis after curative resection in our multivariate regression model (p < 0.001).

Conclusion: Pin1, RhoA and RhoC co-overexpressions are prognostic factor for metastatic HCC and predict poor recurrence-free survival.