Open Access Research article

A panel of tumor markers, calreticulin, annexin A2, and annexin A3 in upper tract urothelial carcinoma identified by proteomic and immunological analysis

Chih-Ming Lu1, Jen-Jie Lin2, Han-Hsiang Huang3, Ying-Chin Ko4, Jue-Liang Hsu5, Jiing-Chuan Chen6, Zhong-Hao Din7 and Yu-Jen Wu3*

Author Affiliations

1 Department of Urology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan

2 Graduate Institute of Veterinary Medicine, National Pingtung University of Science and Technology, Pingtung, Taiwan

3 Department of Beauty Science, Meiho University, Pingtung, Taiwan

4 Institute of Medicine, China Medical University, Taichung, Taiwan

5 Graduate Institute of Biotechnology, National Pingtung University of Science and Technology, Pingtung, Taiwan

6 Department of Food Science and Nutrition, Meiho University, Pingtung, Taiwan

7 Graduate Institute of Applied Healthy and Biotechnology, Meiho University, Pingtung, Taiwan

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BMC Cancer 2014, 14:363  doi:10.1186/1471-2407-14-363

Published: 23 May 2014

Abstract

Background

Upper tract urothelial carcinoma (UTUC) is a tumor with sizable metastases and local recurrence. It has a worse prognosis than bladder cancer. This study was designed to investigate the urinary potential tumor markers of UTUC.

Methods

Between January 2008 and January 2009, urine was sampled from 13 patients with UTUC and 20 healthy adults. The current study identified biomarkers for UTUC using non-fixed volume stepwise weak anion exchange chromatography for fractionation of urine protein prior to two-dimensional gel electrophoresis.

Results

Fifty five differential proteins have been determined by comparing with the 2-DE maps of the urine of UTUC patients and those of healthy people. Western blotting analysis and immunohistochemistry of tumor tissues and normal tissues from patients with UTUC were carried out to further verify five possible UTUC biomarkers, including zinc-alpha-2-glycoprotein, calreticulin, annexin A2, annexin A3 and haptoglobin. The data of western blot and immunohistochemical analysis are consistent with the 2-DE data. Combined the experimental data in the urine and in tumor tissues collected from patients with UTUC, the crucial over-expressed proteins are calreticulin, annexin A2, and annexin A3.

Conclusions

Calreticulin, annexin A2, and annexin A3 are very likely a panel of biomarkers with potential value for UTUC diagnosis.

Keywords:
Upper tract urothelial carcinoma; Proteomic; Urine; Annexin A2; Annexin A3; Calreticulin; Zn-alpha-2-glycoprotein