Department of Medical Informatics, Medical College of Nantong University, Nantong, China; Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, No. 20 West Temple Rd, Nantong 226001, China.
Department of Immunology, Medical College of Nantong University, Nantong, China.
Hepatobiliary Pancreat Dis Int. 2018 Jun;17(3):227-232. doi: 10.1016/j.hbpd.2018.03.005. Epub 2018 Mar 13.
Wingless-type MMTV integration site family member 5a (Wnt5a) is involved in carcinogenesis. However, little data are available in Wnt5a signaling with hepatocellular carcinoma (HCC). In the present study, we investigated the expression of hepatic Wnt5a in HCC and the role of Wnt5a in HCC progression and outcome.
Wnt5a expression and cellular distribution in HCCs and their matched paracancerous tissues from 87 patients were analyzed with tissue microarray and immunohistochemistry and compared with hepatic Wnt3a signaling. Wnt5a expression was categorized into low or high based on immunohistochemistry. Overall survival rate of HCC patients was estimated in correlation with the hepatic Wnt5a level using Kaplan-Meier method; the survival difference between patients with low and those with high Wnt5a was compared with log-rank test; and prognostic analysis was carried out with Cox regression.
Total incidence of Wnt5a expression in the HCC tissues was 70.1%, which was significantly lower (χ= 13.585, P < 0.001) than that in their paracancerous tissues (88.5%). Significant difference of Wnt5a intensity was found between HCC and their paracancerous tissues (Z = 8.463, P < 0.001). Wnt5a intensity was inversely correlated with Wnt3a signaling (r = -0.402, P < 0.001) in HCC tissues. A decrease of Wnt5a expression in relation to the clinical staging from stage I to IV and low or no staining at advanced HCC were observed. Wnt5a level was related to periportal embolus (χ= 11.069, P < 0.001), TNM staging (χ= 8.852, P < 0.05), 5-year survival (χ= 4.961, P < 0.05), and confirmed as an independent prognosis factor of HCC patients (hazard ratio: 1.957; 95% confidence interval: 1.109-3.456; P < 0.05).
The decrease of hepatic Wnt5a signaling is associated with HCC progression and poor prognosis.
无翅型 MMV 整合位点家族成员 5a（Wnt5a）参与了致癌作用。然而，关于 Wnt5a 信号与肝细胞癌（HCC）的相关数据很少。本研究旨在探讨 HCC 中肝 Wnt5a 的表达及其在 HCC 进展和预后中的作用。
采用组织微阵列和免疫组织化学技术分析了 87 例 HCC 及其配对癌旁组织中 Wnt5a 的表达和细胞分布，并与肝 Wnt3a 信号进行了比较。根据免疫组织化学结果，将 Wnt5a 表达分为低表达和高表达。采用 Kaplan-Meier 法估计 HCC 患者的总生存率，并与肝 Wnt5a 水平相关联；采用对数秩检验比较 Wnt5a 低表达和高表达患者的生存差异；采用 Cox 回归进行预后分析。
HCC 组织中 Wnt5a 的总表达率为 70.1%，显著低于癌旁组织（88.5%）（χ=13.585，P<0.001）。HCC 组织与癌旁组织之间的 Wnt5a 强度存在显著差异（Z=8.463，P<0.001）。在 HCC 组织中，Wnt5a 强度与 Wnt3a 信号呈负相关（r=-0.402，P<0.001）。随着临床分期从 I 期到 IV 期的进展，Wnt5a 的表达逐渐降低，晚期 HCC 中低表达或无表达。Wnt5a 水平与门脉周围栓塞（χ=11.069，P<0.001）、TNM 分期（χ=8.852，P<0.05）、5 年生存率（χ=4.961，P<0.05）有关，且被证实为 HCC 患者的独立预后因素（危险比：1.957；95%置信区间：1.109-3.456；P<0.05）。
肝 Wnt5a 信号的降低与 HCC 的进展和不良预后有关。
