A1 Refereed original research article in a scientific journal
Exosomal miRNAs from neutrophils act as accurate biomarkers for gastric cancer diagnosis
Authors: Yu Dan, Zhang Jiahui, Wang Maoye, Ji Runbi, Qian Hui, Xu Wenrong, Zhang Hongbo, Gu Jianmei, Zhang Xu
Publisher: Elsevier B.V.
Publication year: 2024
Journal: Clinica Chimica Acta
Journal name in source: Clinica Chimica Acta
Volume: 554
eISSN: 1873-3492
DOI: https://doi.org/10.1016/j.cca.2024.117773
Web address : https://doi.org/10.1016/j.cca.2024.117773
Self-archived copy’s web address: https://research.utu.fi/converis/portal/detail/Publication/387199996
Background:
Gastric cancer (GC) is the third leading cause of cancer-related death worldwide. Sensitive and accurate biomarkers can greatly aid in early diagnosis and favorable prognosis. Neutrophils are the most abundant immune cells in human circulation and play a critical role in tumor progression. Neutrophil-derived exosomes (Neu-Exo) contain abundant bioactive molecules and are critically involved in disease progression.
Methods:
We proposed a Dynabeads-based (CD66b antibody-coupled) separation and detection system for Neu-Exo analysis. Dual antibody-assisted fluorescent Dynabeads was established to detect Neu-Exo abundance. MiRNA signature of Neu-Exo was identified by RNA sequencing. QRT-PCR and droplet digital PCR (ddPCR) were used for candidate miRNA detection and the potential of Neu-Exo miRNAs in the diagnosis of gastric cancer was evaluated.
Results:
Dual antibody-assisted fluorescent Dynabeads obtained a detection limit of 7.8 × 105 particles/mL of Neu-Exo and a recovery rate of 81 % under optimized conditions. ROC curve indicated that the abundance of CD66b+ Neu-Exo could well distinguish GC patients from healthy controls (HC) (AUC > 0.8). Additionally, miR-223-3p was found among the top differentially expressed miRNAs in Neu-Exo and presented superior diagnostic value in gastric cancer. Droplet digital PCR (ddPCR) significantly improved the diagnostic efficiency to differentiate GC patients from HC and benign gastric diseases (BGD) patients (AUC > 0.9).
Conclusion:
The Dynabeads-based separation and detection system, assisted with ddPCR analysis, provides a promising platform to enrich Neu-Exo and analyze miRNA profile for gastric cancer liquid biopsy.
Downloadable publication This is an electronic reprint of the original article. |