Fahiemeh Bahramnejad,1Dorna Dehghani,2Mojtaba Mortazavi,3,*
1. Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran 2. Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran 3. Department of Biotechnology, Institute of Science and High Technology and Environmental Sciences, Graduate University of Advanced Technology, Kerman, Iran
Introduction: The tumors generally refer to a set of diseases in which growth and proliferation occur out of the control of cells. Tumors are divided into benign and malignant. Benign tumors do not spread throughout the body, are not dangerous, and are not considered cancerous. But in malignant tumors, cells migrate and invade other parts of the body, infecting them as well. These types of tumors are dangerous and are considered cancers. Cancer is one of the leading causes of death worldwide and only small improvements have been made in reducing its mortality. Today, there are various methods for treating cancers, but most of them, in addition to killing cancer cells, also damage healthy cells. Breast cancer is the most common non-skin cancer among women and the second leading cause of cancer death in the world. According to the latest Globocan statistics in 2012, the prevalence of breast cancer in the world is 1671 thousand cases, while 39% of diagnosed cases were in Asian countries. One of the causes of breast cancer is mutations in the P53 gene. The p53 protein is a transcription factor that controls downstream target genes that control cellular functions, including cell cycle, apoptosis, and cell aging. Wild-type p53 has a DNA replication function. The TP53 tumor suppressor gene was known 40 years ago. As one of the most important transcription factors regulating cancer cells, this protein plays a broad regulatory role in gene expression, DNA repair, metabolism, cell survival, cell cycle regulation, apoptosis, and aging. Some p53 (mtp53) mutant proteins have an oncogenic function (GOF) that enhances tumor growth, genomic instability, invasion, cancer resistance, and diverse proteomic and metabolic pathways.
Methods: For breast cancer vaccine design, these vaccines were first reviewed at the vaxquery site. Examining the P53 and Tp53 proteins at the vaxijen site, we concluded that P53 with a probability of 0.5583 and Tp53 with a probability of 0.7117 could be a suitable antigen for the design of a breast cancer vaccine. We then tested the allergen of both proteins at the Aller topp.server site and found that Tp53 is an allergen. So Tp53 is not a good antigen, but P53 is not an allergen and is not toxic, so it is a good factor for vaccine design. With the help of IEBD, PROPRED, and ABCPRED sites, the appropriate epitope was selected and designed. The structure designed at the prabi and swiss model sites was investigated and finally, the interaction between receptor and ligand was investigated using HEX software and BSA was used as a control sample.
Results: Based on our studies, we found that P53 protein is a suitable factor for vaccine design in terms of toxicity, allergen, and density. Based on modeling and reviews, the HLA-DRB1-01: 01 receptor connects well with the designed ligand, and the receptor and ligand are well selected and designed.
Conclusion: Any change in the P53 protein can cause cancer, and since this protein is present in most cells and is involved in cell proliferation, it is a common factor among all cells and may cause cancer. Therefore, if the vaccine is based on this protein, it can be said that a factor has been found to fight most cancers.