Serum Anti-BRAT1 is a Common Molecular Biomarker for Gastrointestinal Cancers and Atherosclerosis

Abstract

Atherosclerosis (AS) and cancers are major global causes of mortality and morbidity. They also share common modifiable pathogenesis risk factors. As the same strategies used to predict AS could also detect certain cancers, we sought novel serum antibody biomarkers of cancers in atherosclerotic sera sampled by liquid biopsy. Using serological antigen identification by cDNA expression cloning (SEREX) and western blot, we screened and detected the antigens BRCA1-Associated ATM Activator 1 (BRAT1) and WD Repeat Domain 1 (WDR1) in the sera of patients with transient ischemic attacks (TIA). Amplified luminescence proximity homogeneous assay-linked immunosorbent assay (AlphaLISA) established the upregulation of serum BRAT1 antibody (BRAT1-Abs) and WDR1 antibody (WDR1-Abs) in patients with AS-related diseases compared with healthy subjects. ROC and Spearman’s correlation analyses showed that BRAT1-Abs and WDR1-Abs could detect AS-related diseases. Thus, serum BRAT1-Abs and WDR1-Abs are potential AS biomarkers. We used online databases and AlphaLISA detection to compare relative antigen and serum antibody expression and found high BRAT1 and BRAT1-Abs expression in patients with GI cancers. Significant increases (> 0.6) in the AUC for BRAT1-Ab vs. esophageal squamous cell carcinoma (ESCC), gastric cancer, and colorectal cancer suggested that BRAT1-Ab exhibited better predictive potential for GI cancers than WDR1-Ab. There was no significant difference in overall survival (OS) between BRAT1-Ab groups (P = 0.12). Nevertheless, a log-rank test disclosed that the highest serum BRAT1-Ab levels were associated with poor ESCC prognosis at 5–60 weeks post-surgery. We validated the foregoing conclusions by comparing serum BRAT1-Ab and WDR1-Ab levels based on the clinicopathological characteristics of the patients with ESCC. Multiple statistical approaches established a correlation between serum BRAT1-Ab levels and platelet counts. BRAT1-Ab upregulation may enable early detection of AS and GI cancers and facilitate the delay of disease progression. Thus, BRAT1-Ab is a potential antibody biomarker for the diagnosis of AS and GI cancers and strongly supports the routine clinical application of liquid biopsy in chronic disease detection and diagnosis.

The combination of positive anti‑WDR1 antibodies with negative anti‑CFL1 antibodies in serum is a poor prognostic factor for patients with esophageal carcinoma

“…Identification of WDR1 and CFL1 using SEREX screening. WDR1 was identified using large-scale SEREX screening with the sera of patients with a transient ischemic attack as an antigen recognized by serum IgG antibodies (13). The 172-1233 region of WDR1 cDNA (accession no.…”

“…WD repeat-containing protein 1 (WDR1; also known as actin-interacting protein 1) regulates cofilin activity, promotes cytoskeletal remodeling, and thus facilitates cell migration and invasion (12). The presence of autoantibodies against WDR1 has been found in the sera of patients who have suffered a transient ischemic attack using SEREX screening (13). The…”

One-step preparation of PEG segment-functionalized polystyrene microspheres and their application as latex in LOCI

“…Finally, the incomplete reaction was removed by silica gel chromatography (n-hexane and methanol : dichloromethane = 1 : 8), followed by spin evaporation of the product dried with anhydrous Na 2 SO 4 to give a clear, pale yellow oily compound. 1 H NMR (600 MHz, CDCl 3 ) d 7.39-7.28 (m, 4H), 6.70 (dd, J = 17.6, 10.9 Hz, 1H), 5.73 (d, J = 17.6 Hz, 1H), 5.22 (dd, J = 10.9, 2.1 Hz, 1H), 4.54 (s, 2H), 3.75-3.57 (m, 17H).…”

“…As one of the sensitive homogeneous chemiluminescence immunoassays, the luminescent oxygen channeling assay (LOCI), which combines the principles of latex agglutination and channeling, has been widely used to detect biomarkers, [1][2][3][4] kinases [5][6][7] and antigens and antibodies [8][9][10][11] since its principle was first proposed by Edwin F. Ullman et al in 1996. 12 In comparison with other sensitive homogeneous immunoassay methodology, LOCI is a homogeneous immunological detection technique using donor microspheres and acceptor microspheres as carriers.…”

Atherosclerosis-related biomarker PABPC1 predicts pan-cancer events

“…Among them, low-density lipoprotein receptor-related protein-associated protein 1 (LRPAP1) played an important role in AS and digestive organ cancers, 25 and BRCA1-associated ATM activator 1 (BRAT1) was significant for gastrointestinal cancers and AS. 26 These common factors suggested that markers associated with AS might also be important in predicting the occurrence of cancer, but the discovery of common markers between them remained insufficient. Meanwhile, biomarkers found in our previous studies were based only on digestive system cancers, and studies using AS serum screening to identify pan-cancer markers were still limited.…”