Yang Xiao-Yu, Wu Bin, Ma Sen-Lin, Yin Lei, Wu Meng-Chao, Li Ai-Jun
1 Division of Special Treatment II, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
2 Department of Surgery, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, China.
Technol Cancer Res Treat. 2018 Jan 1;17:1533033818794190. doi: 10.1177/1533033818794190.
ZW10 interactor was recently reported to correlate with human cancers. However, the prognostic value of ZW10 interactor in hepatocellular carcinoma was not reported.
The expression level of ZW10 interactor was evaluated by Western blot and immunohistochemistry using tissue microarray. In the present study, we used 5 pairs of hepatocellular carcinoma and peritumoral frozen tissues for Western blot, and 70 paired paraffin-embedded hepatocellular carcinoma and peritumoral tissues as expression pattern cohort (cohort 1), and 280 paraffin-embedded hepatocellular carcinoma tissues were used as prognostic cohort (cohort 2). The integral optic density representing the expression level of ZW10 interactor in each tissue sample, was calculated using Image-Pro Plus. The integral optic density was added to the X-tile software for calculating the outcome-based cut point. Kaplan-Meier and Cox regression were used to evaluate the prognostic values.
The expression level ZW10 interactor was decreased in hepatocellular carcinoma tissues in 85.7% (60/70) of the cases compared to the corresponding peritumoral tissues evaluated by immunohistochemistry. Similar result was obtained by Western blot analysis using frozen tissue. Expression of ZW10 interactor was closely correlated with age ( P = .0001) and liver cirrhosis in cohort 1 and tumor node metastasis ( P = .018), tumor size ( P = .005), and vascular invasion ( P = .022) in cohort 2 based on χ analyses. Survival analyses indicated that patients with hepatocellular carcinoma having low ZW10 interactor expression had a shorter overall survival time and time to recurrence compared to cases with high ZW10 interactor expression in the prognostic cohort ( P < .0001 for both overall survival and time to recurrence ). Univariate and multivariate Cox analyses indicated that ZW10 interactor was an independent prognostic factor for overall survival ( P = .033).
The present study clearly showed that ZW10 interactor was frequently decreased in hepatocellular carcinoma compared to nontumoral liver tissues, and ZW10 interactor could serve as a potential prognostic marker in patients with hepatocellular carcinoma after surgery.
最近有报道称ZW10相互作用分子与人类癌症相关。然而,ZW10相互作用分子在肝细胞癌中的预后价值尚未见报道。
采用蛋白质免疫印迹法和免疫组织化学方法,利用组织芯片评估ZW10相互作用分子的表达水平。在本研究中,我们使用5对肝细胞癌及癌旁冷冻组织进行蛋白质免疫印迹分析,70对石蜡包埋的肝细胞癌及癌旁组织作为表达模式队列(队列1),280例石蜡包埋的肝细胞癌组织作为预后队列(队列2)。使用Image-Pro Plus软件计算每个组织样本中代表ZW10相互作用分子表达水平的积分光密度。将积分光密度输入X-tile软件以计算基于结果的切点。采用Kaplan-Meier法和Cox回归分析评估预后价值。
免疫组织化学评估显示,与相应癌旁组织相比,85.7%(60/70)的肝细胞癌组织中ZW10相互作用分子的表达水平降低。使用冷冻组织进行蛋白质免疫印迹分析也得到了类似结果。基于χ分析,队列1中ZW10相互作用分子的表达与年龄(P = 0.0001)和肝硬化密切相关,队列2中与肿瘤淋巴结转移(P = 0.018)、肿瘤大小(P = 0.005)及血管侵犯(P = 0.022)密切相关。生存分析表明,在预后队列中,与ZW10相互作用分子高表达的肝细胞癌患者相比,ZW10相互作用分子低表达的患者总生存时间和复发时间更短(总生存和复发时间的P均<0.0001)。单因素和多因素Cox分析表明,ZW10相互作用分子是总生存的独立预后因素(P = 0.033)。
本研究清楚地表明,与非肿瘤性肝组织相比,肝细胞癌中ZW10相互作用分子的表达经常降低,且ZW10相互作用分子可作为肝细胞癌患者术后潜在的预后标志物。