Original Article
Copyright ©2012 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. May 7, 2012; 18(17): 2053-2060
Published online May 7, 2012. doi: 10.3748/wjg.v18.i17.2053
Affinity peptide developed by phage display selection for targeting gastric cancer
Wen-Jie Zhang, Yan-Xia Sui, Arun Budha, Jian-Bao Zheng, Xue-Jun Sun, Ying-Chun Hou, Thomas D Wang, Shao-Ying Lu
Wen-Jie Zhang, Yan-Xia Sui, Arun Budha, Jian-Bao Zheng, Xue-Jun Sun, Shao-Ying Lu, Department of General Surgery, The First Affiliated Hospital of Medical School, Xian Jiaotong University, Xi’an 710061, Shaanxi Province, China
Wen-Jie Zhang, The Third Hospital of Chengdu, Chengdu 610031, Sichuan Province, China
Ying-Chun Hou, Shaanxi Normal University, Xi’an 710061, Shaanxi Province, China
Thomas D Wang, Department of Medicine, Division of Gastroenterology and Hepatology, School of Medicine, University of Michigan, Ann Arbor, MI 48109, United States
Author contributions: Zhang WJ, Sun XJ, Hou YC, Wang TD and Lu SY designed the research; Zhang WJ, Sui YX, Budha A, Zheng JB and Lu SY performed the experiments; Zhang WJ and Lu SY analyzed the data; Zhang WJ, Wang TD and Lu SY wrote the paper.
Supported by The National Natural Science Foundation of China, No. 81172359
Correspondence to: Shao-Ying Lu, MD, PhD, Department of General Surgery, The First Affiliated Hospital of Medical School, Xian Jiaotong University, Xi’an 710061, Shaanxi Province, China. robertlu@mail.xjtu.edu.cn
Telephone: +86-29-85323875  Fax: +86-29-85324149
Received: November 29, 2011
Revised: February 6, 2012
Accepted: February 16, 2012
Published online: May 7, 2012
Abstract

AIM: To develop an affinity peptide that binds to gastric cancer used for the detection of early gastric cancer.

METHODS: A peptide screen was performed by biopanning the PhD-12 phage display library, clearing non-specific binders against tumor-adjacent normal appearing gastric mucosa and obtaining selective binding against freshly harvested gastric cancer tissues. Tumor-targeted binding of selected peptides was confirmed by bound phage counts, enzyme-linked immunosorbent assay, competitive inhibition, fluorescence microscopy and semi-quantitative analysis on immunohistochemistry using different types of cancer tissues.

RESULTS: Approximately 92.8% of the non-specific phage clones were subtracted from the original phage library after two rounds of biopanning against normal- appearing gastric mucosa. After the third round of positive screening, the peptide sequence AADNAKTKSFPV (AAD) appeared in 25% (12/48) of the analyzed phages. For the control peptide, these values were 6.8 ± 2.3, 5.1 ± 1.7, 3.5 ± 2.1, 4.6 ± 1.9 and 1.1 ± 0.5, respectively. The values for AAD peptide were statistically significant (P < 0.01) for gastric cancer as compared with other histological classifications and control peptide.

CONCLUSION: A novel peptide is discovered to have a specific binding activity to gastric cancer, and can be used to distinguish neoplastic from normal gastric mucosa, demonstrating the potential for early cancer detection on endoscopy.

Keywords: Gastric cancer, Peptide, Phage library, Molecular imaging, Early detection, Immunohistochemistry, Enzyme-linked immunosorbent assay