Han Wei, Zhang Cong, Gao Xiao-Jiao, Wang Hua-Bing, Chen Fang, Cao Fang, Hu Yong-Wei, Ma Jun, Gu Xing, Ding Hou-Zhong
Department of General Surgery, Kunshan First People's Hospital Affiliated to Jiangsu University, Kunshan, China.
Department of Pharmacy, Kunshan Hospital of Traditional Chinese Medicine, Kunshan, China.
J Breast Cancer. 2018 Mar;21(1):51-61. doi: 10.4048/jbc.2018.21.1.51. Epub 2018 Mar 23.
Five members of the zinc finger of the cerebellum (ZIC) family-ZIC1, ZIC2, ZIC3, ZIC4, and ZIC5-have been shown to be involved in various carcinomas. Here, we aimed to explore the clinicopathologic and prognostic roles of ZIC family members in invasive breast cancer patients using immunohistochemical analysis, western blotting analysis, and real-time quantitative polymerase chain reaction (RT-qPCR).
A total of 241 female invasive breast cancer patients who underwent radical mastectomy between 2009 and 2011 were enrolled. ZIC proteins in 241 pairs of breast tumors and corresponding normal tissues were investigated using immunohistochemistry and the clinicopathologic roles of proteins were analyzed using Pearson's chi-square test. Kaplan-Meier curves and Cox regression analysis were also used to analyze the prognostic value of the ZIC proteins. In addition, 12 pairs of fresh-frozen breast tumors and matched normal tissues were used in the western blotting analysis and RT-qPCR.
Only ZIC1 expression in normal tissues was obviously higher than that in tumors (<0.001). On multivariate analysis, ZIC1 expression (in overall survival analysis: hazard ratio [HR], 0.405, 95% confidence interval [CI], 0.233-0.702, =0.001; in disease-free survival analysis: HR, 0.395, 95% CI, 0.234-0.669, =0.001) was identified as a prognostic indicator of invasive breast cancer.
ZIC1, but not the other proteins, was obviously decreased in breast tumors and associated with clinicopathologic factors. Thus, ZIC1 might be a novel indicator to predict the overall and disease-free survival of invasive breast cancer patients.
小脑锌指蛋白（ZIC）家族的5个成员——ZIC1、ZIC2、ZIC3、ZIC4和ZIC5——已被证明与多种癌症有关。在此，我们旨在通过免疫组织化学分析、蛋白质印迹分析和实时定量聚合酶链反应（RT-qPCR），探讨ZIC家族成员在浸润性乳腺癌患者中的临床病理及预后作用。
共纳入2009年至2011年间接受根治性乳房切除术的241例女性浸润性乳腺癌患者。采用免疫组织化学方法检测241对乳腺肿瘤及相应正常组织中的ZIC蛋白，并使用Pearson卡方检验分析蛋白的临床病理作用。还采用Kaplan-Meier曲线和Cox回归分析来分析ZIC蛋白的预后价值。此外，在蛋白质印迹分析和RT-qPCR中使用了12对新鲜冷冻的乳腺肿瘤及匹配的正常组织。
仅正常组织中的ZIC1表达明显高于肿瘤组织（<0.001）。多因素分析显示，ZIC1表达（总生存分析：风险比[HR]，0.405，95%置信区间[CI]，0.233 - 0.702，P = 0.001；无病生存分析：HR，0.395，95% CI，0.234 - 0.669，P = 0.001）被确定为浸润性乳腺癌的预后指标。
ZIC1在乳腺肿瘤中明显降低，且与临床病理因素相关，而其他蛋白则不然。因此，ZIC1可能是预测浸润性乳腺癌患者总生存和无病生存的新指标。
