J Cancer 2017; 8(15):3062-3069. doi:10.7150/jca.19619

Research Paper

Identification of Nucleobindin-2 as a Potential Biomarker for Breast Cancer Metastasis Using iTRAQ-based Quantitative Proteomic Analysis

Liang Zeng1, 2*, Jingmin Zhong2*, Guangchun He3, Fangjun Li4, Jing Li5, Wen Zhou6, Wenbin Liu2, Yun Zhang2, Sanqian Huang2, Zhihong Liu2, Xiyun Deng3✉

1. Department of Pathology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong 510623, China;
2. Department of Pathology, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China;
3. Department of Pathology, Hunan Normal University Medical College, Changsha, Hunan 410013, China;
4. Department of Social Medicine, Hunan Provincial People's Hospital & The Affiliated Hospital of Hunan Normal University, Changsha, Hunan 410007, China;
5. Department of Breast Internal Medicine, Hunan Cancer Hospital & The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan 410013, China;
6. Key Laboratory of Cancer of the Ministry of Health, Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 4100078, China.
* Liang Zeng and Jingmin Zhong contributed equally to this work.

Abstract

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 (n = 106). The relationship between NUCB2 expression and the clinicopathological characteristics of breast cancer patients (n = 189) were analyzed by χ2 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 (P = 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 (P = 0.004). Cox regression model suggested that NUCB2 was a risk factor of breast cancer patients (P = 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.

Keywords: Breast cancer, Metastasis, Prognosis, iTRAQ, Nucleobindin-2.

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How to cite this article:
Zeng L, Zhong J, He G, Li F, Li J, Zhou W, Liu W, Zhang Y, Huang S, Liu Z, Deng X. Identification of Nucleobindin-2 as a Potential Biomarker for Breast Cancer Metastasis Using iTRAQ-based Quantitative Proteomic Analysis. J Cancer 2017; 8(15):3062-3069. doi:10.7150/jca.19619. Available from http://www.jcancer.org/v08p3062.htm