Zeng Liang, Zhong Jingmin, He Guangchun, Li Fangjun, Li Jing, Zhou Wen, Liu Wenbin, Zhang Yun, Huang Sanqian, Liu Zhihong, Deng Xiyun
Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China.
Department of Pathology, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China.
J Cancer. 2017 Sep 2;8(15):3062-3069. doi: 10.7150/jca.19619. eCollection 2017.
Metastasis is a lethal step in the progression of breast cancer. None of the metastasis-associated biomarkers identified up to now has a definite prognostic value in breast cancer patients. This study was designed to identify biomarkers for breast cancer metastasis and predictors of the prognosis of breast cancer patients. The differentially expressed proteins between 23 paired primary breast tumor and metastatic lymph nodes were identified by quantitative iTRAQ proteomic analysis. Immunohistochemistry was applied to locate and assess the expression of NUCB2 in paired primary breast tumor and metastatic lymph node tissues ( = 106). The relationship between NUCB2 expression and the clinicopathological characteristics of breast cancer patients ( = 189) were analyzed by χ test. Kaplan-Meier analysis and Cox hazard regression analysis were utilized to investigate the relationship between its expression and prognosis of breast cancer patients. The iTRAQ proteomic results showed that 4,837 confidential proteins were identified, 643 of which were differentially expressed in the primary breast cancer tissues and the paired metastatic lymph nodes. NUCB2 protein was found decreased in paired metastatic lymph nodes ( = 0.000), with the positive expression rate being 82% in primary breast cancer tissues and 47% in paired metastatic lymph nodes, respectively. According to Kaplan-Meier analysis, the overall survival time of patients with positive expression of NUCB2 protein were shorter than those with negative NUCB2 expression ( = 0.004). Cox regression model suggested that NUCB2 was a risk factor of breast cancer patients ( = 0.045, RR = 1.854). We conclude that NUCB2 can be used as a potential biomarker for breast cancer metastasis and a prognostic predictor of breast cancer patients.
转移是乳腺癌进展中的致命步骤。迄今为止所鉴定出的与转移相关的生物标志物，在乳腺癌患者中均无明确的预后价值。本研究旨在鉴定乳腺癌转移的生物标志物以及乳腺癌患者预后的预测指标。通过定量iTRAQ蛋白质组学分析，鉴定了23对原发性乳腺肿瘤和转移淋巴结之间差异表达的蛋白质。应用免疫组织化学方法定位并评估NUCB2在106对原发性乳腺肿瘤和转移淋巴结组织中的表达。采用χ检验分析NUCB2表达与189例乳腺癌患者临床病理特征之间的关系。利用Kaplan-Meier分析和Cox风险回归分析研究其表达与乳腺癌患者预后的关系。iTRAQ蛋白质组学结果显示，共鉴定出4837种可信蛋白质，其中643种在原发性乳腺癌组织和配对的转移淋巴结中差异表达。发现NUCB2蛋白在配对的转移淋巴结中减少（P = 0.000），其在原发性乳腺癌组织中的阳性表达率为82%，在配对的转移淋巴结中为47%。根据Kaplan-Meier分析，NUCB2蛋白表达阳性患者的总生存时间短于NUCB2表达阴性患者（P = 0.004）。Cox回归模型表明，NUCB2是乳腺癌患者的一个危险因素（P = 0.045，RR = 1.854）。我们得出结论，NUCB2可作为乳腺癌转移的潜在生物标志物和乳腺癌患者的预后预测指标。
