Bioinformatics-based screening and prediction of compounds and antigen epitopes for immune targets with point mutations in colitis-associated colorectal cancer
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Updated: Jul 17, 2026
Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing
Published on: September 25, 2011
Xinyi Peng1, Quan Sun2, Dongli Zhao3
1Department of Oncology, Wenzhou TCM Hospital of Zhejiang Chinese Medical University, No. 9 Jiaowei Road, Wenzhou, 325000, Zhejiang, China.
Objective:
This study aimed to identify and predict bioactive small molecules and immunogenic antigen epitopes targeting proteins with point mutations in colitis-associated colorectal cancer (CAC), using integrative bioinformatics approaches.
Methods:
Genes associated with colorectal cancer (CRC), ulcerative colitis (UC), diabetes mellitus (DM), hyperlipidemia (HL), gout, and functional dyspepsia (FD) were obtained from disease databases and GEO. Overlapping genes were identified using jvenn. CIBERSORT was used for immune infiltration analysis. Prognostic significance was evaluated using KM Plotter, and gene co-expression correlations in CRC were assessed via TIMER. cBioPortal was employed to analyze mutation profiles, tumor mutational burden (TMB), and microsatellite instability (MSI). Allosteric sites were predicted using AlloDriver. Molecular docking (AutoDock Vina v1.2.3) and 100-ns molecular dynamics simulations (GROMACS v2022.03) assessed protein-ligand interactions. Neoantigen and B-cell epitope immunogenicity were predicted using NetMHCpan-4.1 and IEDB, respectively.
Results:
SERPINE1, SELE, SPP1, PLAU, COL1A1, PTGES, IL6, KDR, and ICAM1 were significantly upregulated in CAC. Lower expression correlated with improved relapse-free and overall survival (log-rank P < 0.05) and was associated with CRC molecular subtypes and biomarkers (P < 0.05). Mutations PLAUY151H, SERPINE1V166A, and KDRP359H were located in allosteric sites. Anacetrapib and LY2090314-metabolism-related compounds-showed high affinity for wild-type KDR, PLAU, and SERPINE1.The KDRP359H and PLAUY151H significantly weakened LY2090314 binding, and SERPINE1V166A mutation significantly reduced Anacetrapib binding, whereas SERPINE1V166A significantly enhanced LY2090314 binding. Although HLA-I affinity of mutation-derived antigens was low, four mutated B-cell epitopes (COL1A1R493H, KDRP551S, ICAM1T1259M, KDRT1260M) exhibited higher immunogenicity than wild-type, suggesting potential for antibody-based therapy.
Conclusion:
Based on bioinformatics analysis, this study identified nine genes significantly upregulated in CAC and associated with prognosis. Allosteric-site mutations in PLAU, SERPINE1, and KDR affect the binding stability of small-molecule drugs (Anacetrapib, LY2090314), suggesting their role in drug response. Four mutation-specific B-cell epitopes (COL1A1R493H, KDRP551S, ICAM1T1259M, KDRT1260M) exhibit enhanced immunogenicity, indicating potential for antibody-based therapy.
Insights
This study identified nine genes upregulated in colitis-associated colorectal cancer (CAC) and found that mutations in PLAU, SERPINE1, and KDR affect drug binding. Four mutated B-cell epitopes show enhanced immunogenicity for potential antibody therapy.
Area of Science:
- Oncology
- Bioinformatics
- Immunology
Background:
- Colitis-associated colorectal cancer (CAC) presents unique challenges in treatment.
- Identifying novel therapeutic targets, including small molecules and immunogenic epitopes, is crucial for improving patient outcomes.
Purpose of the Study:
- To identify and predict bioactive small molecules and immunogenic antigen epitopes targeting mutated proteins in CAC using integrative bioinformatics.
- To analyze gene expression, mutations, and immune infiltration in CAC to uncover potential therapeutic targets.
Main Methods:
- Utilized disease databases and gene expression data to identify overlapping genes in CAC.
- Performed immune infiltration analysis, survival analysis, and mutation profiling (TMB, MSI).
- Predicted allosteric sites, performed molecular docking and dynamics simulations, and assessed neoantigen and B-cell epitope immunogenicity.
Main Results:
- Identified nine significantly upregulated genes in CAC (SERPINE1, SELE, SPP1, PLAU, COL1A1, PTGES, IL6, KDR, ICAM1), with lower expression correlating with improved survival.
- Discovered allosteric site mutations (PLAUY151H, SERPINE1V166A, KDRP359H) affecting small-molecule drug binding (Anacetrapib, LY2090314).
- Identified four mutation-specific B-cell epitopes with enhanced immunogenicity, suggesting potential for antibody-based therapies.
Conclusions:
- Bioinformatics analysis revealed nine prognostic genes in CAC and highlighted the impact of specific mutations on drug response.
- Mutation-specific B-cell epitopes demonstrate enhanced immunogenicity, offering a promising avenue for developing novel antibody-based therapies for CAC.
