title: Diagnostic potential of zinc finger protein-specific autoantibodies and associated linear B-cell epitopes in colorectal cancer.
abstract: Colorectal cancer is one of the most common cancers worldwide with almost 700,000 deaths every year. Detection of colorectal cancer at an early stage significantly improves patient survival. Cancer-specific autoantibodies found in sera of cancer patients can be used for pre-symptomatic detection of the disease. In this study we assess the zinc finger proteins ZNF346, ZNF638, ZNF700 and ZNF768 as capture antigens for the detection of autoantibodies in colorectal cancer. Sera from 96 patients with colorectal cancer and 35 control patients with no evidence of cancer on colonoscopy were analysed for the presence of ZNF-specific autoantibodies using an indirect ELISA. Autoantibodies to individual ZNF proteins were detected in 10-20% of colorectal cancer patients and in 0-5.7% of controls. A panel of all four ZNF proteins resulted in an assay specificity of 91.4% and sensitivity of 41.7% for the detection of cancer patients in a cohort of non-cancer controls and colorectal cancer patients. Clinicopathological and survival analysis revealed that ZNF autoantibodies were independent of disease stage and did not correlate with disease outcome. Since ZNF autoantibodies were shared between patients and corresponding ZNF proteins showed similarities in their zinc finger motifs, we performed an in silico epitope sequence analysis. Zinc finger proteins ZNF700 and ZNF768 showed the highest sequence similarity with a bl2seq score of 262 (E-value 1E-81) and their classical C2H2 ZNF motifs were identified as potential epitopes contributing to their elevated immunogenic potential. Our findings show an enhanced and specific immunogenicity to zinc finger proteins, thereby providing a multiplexed autoantibody assay for minimally invasive detection of colorectal cancer.
authors: Biomedical Diagnostics Institute, Dublin City University, Dublin, Ireland.
authors: Julie-Ann
authors: JA
authors: O'Reilly
authors: Biomedical Diagnostics Institute, Dublin City University, Dublin, Ireland.
authors: Jenny
authors: J
authors: Fitzgerald
authors: Biomedical Diagnostics Institute, Dublin City University, Dublin, Ireland; School of Biotechnology, Dublin City University, Dublin, Ireland.
authors: Seán
authors: S
authors: Fitzgerald
authors: Biomedical Diagnostics Institute, Dublin City University, Dublin, Ireland; Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland.
authors: Dermot
authors: D
authors: Kenny
authors: Department of Pathology, Royal College of Surgeons in Ireland and Beaumont Hospital, Dublin, Ireland.
authors: Elaine W
authors: EW
authors: Kay
authors: Biomedical Diagnostics Institute, Dublin City University, Dublin, Ireland; School of Biotechnology, Dublin City University, Dublin, Ireland.
authors: Richard
authors: R
authors: O'Kennedy
authors: Biomedical Diagnostics Institute, Dublin City University, Dublin, Ireland.
authors: Gregor S
authors: GS
authors: Kijanka
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000097:blood* / Q000276:immunology; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000097:blood / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality; D004268:DNA-Binding Proteins / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D018985:Epitopes, B-Lymphocyte / Q000276:immunology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000276:immunology*; D011379:Prognosis; D016601:RNA-Binding Proteins / Q000276:immunology*; D015996:Survival Rate; D014157:Transcription Factors; D016335:Zinc Fingers / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D018985:Epitopes, B-Lymphocyte; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C121935:ZNF346 protein, human; C099656:ZNF638 protein, human