Affinity peptide developed by phage display selection for targeting gastric cancer |
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Authors: | Zhang Wen-Jie Sui Yan-Xia Budha Arun Zheng Jian-Bao Sun Xue-Jun Hou Ying-Chun Wang Thomas D Lu Shao-Ying |
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Affiliation: | Department of General Surgery, The First Affiliated Hospital of Medical School, Xian Jiaotong University, Xi'an 710061, Shaanxi Province, China. |
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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. |
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Keywords: | Gastric cancer Peptide Phage library Molecular imaging Early detection Immunohistochemistry Enzyme-linked immunosorbent assay |
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