Ezediuno Louis Odinakaose, Ockiya Michael Asebake, Awoniyi Luqman Oluwaseun, Sangodare Adeola Oyepeju, David Kehinde Busuyi, Robert Faith Owabhel
Department of Microbiology, University of Benin, Benin City, Nigeria.
Department of Animal Science, Faculty of Agriculture, Niger Delta University, Amassoma, Nigeria.
Korean J Clin Oncol. 2025 Apr;21(1):20-31. doi: 10.14216/kjco.24326. Epub 2025 Apr 30.
Colorectal cancer (CRC) remains a significant global health burden, necessitating innovative approaches for prevention and treatment. This study proposes a multiepitope vaccine targeting carcinoembryonic antigen (CEA) and insulin-like growth factor-1 receptor (IGF-1R), two prominent biomarkers associated with CRC progression.
Sequences of CEA and IGF-1R proteins were retrieved from NCBI databank, the sequences were aligned on the MEGA5 tool to identify conserved regions. Immunological and structural predictive analysis which include antigenic potential prediction, cytotoxic T-lymphocytes (CTLs), helper-T lymphocytes (HTLs), B-cell epitopes predictions, and prediction of the vaccine secondary and tertiary structure were performed. The vaccine was evaluated to validate its physiochemical and immunological properties. To determine the binding energy and domain, the tertiary structure of the vaccine was docked to Toll-like receptor 4, and viewed on PyMOL and LigPlot+ tools.
CEA and IGF-1R were revealed to be highly antigenic, and non-allergens demonstrating the capacity to elicit robust immune responses, which include CTLs, HTLs, and B cells activation. The secondary structure revealed a conformation closely resembling native protein, with alpha helices, beta sheets, and coils, indicative of favorable interactions. Tertiary structure prediction predicted five models, model 0 was selected and validated due its highest confidence, and validation revealed that 87.5% of residues were within favored regions, with a z-score of 4.03. Molecular docking predicted strong binding complex with low binding energy.
Based on our analysis, the proposed multiepitope vaccine holds promise as an effective preventive measure against colorectal cancer development.
结直肠癌（CRC）仍是一项重大的全球健康负担，因此需要创新的预防和治疗方法。本研究提出了一种针对癌胚抗原（CEA）和胰岛素样生长因子-1受体（IGF-1R）的多表位疫苗，这两种是与CRC进展相关的重要生物标志物。
从NCBI数据库检索CEA和IGF-1R蛋白的序列，在MEGA5工具上对序列进行比对以识别保守区域。进行了免疫和结构预测分析，包括抗原潜力预测、细胞毒性T淋巴细胞（CTL）、辅助性T淋巴细胞（HTL）、B细胞表位预测以及疫苗二级和三级结构预测。对该疫苗进行评估以验证其物理化学和免疫学特性。为了确定结合能和结构域，将疫苗的三级结构与Toll样受体4对接，并在PyMOL和LigPlot+工具上查看。
CEA和IGF-1R被发现具有高度抗原性且无过敏原，显示出引发强烈免疫反应的能力，包括CTL、HTL和B细胞激活。二级结构显示出与天然蛋白非常相似的构象，有α螺旋、β折叠和卷曲，表明存在良好的相互作用。三级结构预测得到五个模型，由于模型0的置信度最高而被选中并验证，验证显示87.5%的残基位于有利区域，z评分为4.03。分子对接预测形成具有低结合能的强结合复合物。
基于我们的分析，所提出的多表位疫苗有望成为预防结直肠癌发展的有效措施。
