Department of Surgery, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong.
Centre for Cancer Research, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong.
BMC Cancer. 2019 Jul 19;19(1):713. doi: 10.1186/s12885-019-5919-3.
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.
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.
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).
Pin1, RhoA and RhoC co-overexpressions are prognostic factor for metastatic HCC and predict poor recurrence-free survival.
识别用于早期检测或预测转移的分子标志物对于 HCC 患者术后治疗的管理以及确定抑制 HCC 进展和转移的新治疗靶点都至关重要。在本研究中，我们研究了 Pin1、RhoA 和 RhoC 与 HCC 转移之间的临床相关性及其与 HCC 转移的相关性。
我们使用 139 名患者的原发性 HCC 样本的随机研究设计，确定了 Pin1、RhoA 和 RhoC 的信使 RNA 表达及其预后价值。
我们的研究结果首次证明了 Pin1 在 HCC 转移中的临床相关性。与配对的相邻非肿瘤肝脏相比，HCC 标本中的 Pin1、RhoA 和 RhoC 转录水平显着升高。Pin1 的过表达与 RhoA（R=0.562，p<0.001）和 RhoC（R=0.529，p<0.001）的过表达密切相关，它们的共过表达与转移性 HCC（p=0.000012）和 HCC 患者无复发生存率差（p<0.00001）相关，其预后意义优于单独过表达 Pin1、RhoA 或 RhoC。Pin1+RhoA/RhoC 的共过表达也是我们多变量回归模型中预测根治性切除后转移发展的独立因素（p<0.001）。
Pin1、RhoA 和 RhoC 的共过表达是转移性 HCC 的预后因素，并预测无复发生存率差。
