Development of a novel multiplex beads‐based assay for autoantibody detection for colorectal cancer diagnosis

Abstract

Humoral response in cancer patients can be used for early cancer detection. By screening high-density protein microarrays with sera from colorectal cancer (CRC) patients and controls, we identified 16 tumor-associated antigens (TAAs) exhibiting high diagnostic value. This high number of TAAs requires the development of multiplex assays combining different antigens for a faster and more accurate prediction of CRC. Here, we have developed and optimized a bead-based assay using nine selected TAAs and two controls to provide a multiplex test for early CRC diagnosis. We screened a collection of 307 CRC patients' and control sera with the beads assay to identify and validate the best TAA combination for CRC detection. The multiplex bead-based assay exhibited a similar diagnostic performance to detect the humoral response in comparison to multiple ELISA analyses. After multivariate analysis, a panel composed of GTF2B, EDIL3, HCK, PIM1, STK4, and p53, together with gender and age, was identified as the best combination of TAAs for CRC diagnosis, achieving an AUC of 89.7%, with 66% sensitivity at 90.0% fixed specificity. The model was validated using bootstrapping analysis. In summary, we have developed a novel multiplex bead assay that after validation with a larger independent cohort of sera could be utilized in a high-throughput manner for population screening to facilitate the detection of early CRC patients.

Cost-effectiveness of colorectal cancer screening and treatment methods: Mapping of systematic reviews

“…[ 9 10 11 12 13 ] Colorectal cancer can be diagnosed by taking a sample of the colon through sigmoidoscopy or colonoscopy (COL). [ 14 15 ] Screening is effective to reduce the chance of dying from colorectal cancer, and is recommended to start at the age of 50 and then on an ongoing basis until the age of 75. [ 16 17 18 ] Polyps are removed during COL.[ 19 20 ] Aspirin and othaer anti-inflammatory nonsteroidal drugs may reduce the disease risk.…”

Prognostic value of plasminogen activator inhibitor‐1 in biomarker exploration using multiplex immunoassay in patients with metastatic renal cell carcinoma treated with axitinib

“…The multiplex immunoassay method is a beads array in which various antibodies are loaded on the beads measured by flow cytometry. Previous reports have comprehensively measured angiogenic factors using serum samples from patients with colorectal, ovarian and small cell lung cancer 12‐14 and urine samples from patients with bladder cancer 15,16 . However, few studies have explored biomarkers as predictive factors in patients with metastatic disease using multiplex immunoassay techniques.…”

Evaluation of serum nucleoside diphosphate kinase A for the detection of colorectal cancer

“…In relation to other candidate serum markers, protein panels reached 42% sensitivity for CRC4344 and 9% for AA43, setting specificity to 95%. More recently, serum autoantibody panels reported 10% sensitivity for AN45 and 48% sensitivity for CRC46, both at 90% specificity.…”