Abstract
Cancer remains one of the major causes of death worldwide. Angiogenesis is crucial for the pathogenesis of various human diseases, especially solid tumors. The discovery of anti-angiogenic peptides is a promising therapeutic route for cancer treatment. Thus, reliably identifying anti-angiogenic peptides is extremely important for understanding their biophysical and biochemical properties that serve as the basis for the discovery of new anti-cancer drugs. This study aims to develop an efficient and interpretable computational model called TargetAntiAngio for predicting and characterizing anti-angiogenic peptides. TargetAntiAngio was developed using the random forest classifier in conjunction with various classes of peptide features. It was observed via an independent validation test that TargetAntiAngio can identify anti-angiogenic peptides with an average accuracy of 77.50% on an objective benchmark dataset. Comparisons demonstrated that TargetAntiAngio is superior to other existing methods. In addition, results revealed the following important characteristics of anti-angiogenic peptides: (i) disulfide bond forming Cys residues play an important role for inhibiting blood vessel proliferation; (ii) Cys located at the C-terminal domain can decrease endothelial formatting activity and suppress tumor growth; and (iii) Cyclic disulfide-rich peptides contribute to the inhibition of angiogenesis and cell migration, selectivity and stability. Finally, for the convenience of experimental scientists, the TargetAntiAngio web server was established and made freely available online.
Highlights
Cancer constitutes a group of diseases involving the unregulated proliferation of abnormal cells
Anti-angiogenesis plays a fundamental role in tumor growth, invasion, and metastatic dissemination
Several anti-angiogenic peptides have been developed in order to promote effective cancer treatment as well as enhanced survival rate
Summary
Cancer constitutes a group of diseases involving the unregulated proliferation of abnormal cells. It is capable of both invading surrounding normal tissue and spreading throughout the body via the circulatory or lymphatic system in a process known as metastasis [1]. Angiogenesis is a process by which new blood vessels are formed and it is seen as one of the key processes for the proliferation and metastatic spread of cancer cells. It promotes the circulation of oxygenated blood, supplies nutrients, and removes waste products from the body [5]. The upregulation of the activity of angiogenic factors alone is not enough for the angiogenesis of neoplasm, as anti-angiogenic factors needs to be downregulated [6]
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