Circulating Gastric Cancer Stem Cells as Blood Screening and Prognosis Factor in Gastric Cancer.

Abstract

Gastric cancer (GC) is the fourth leading cause of cancer-related death, associated with late diagnosis and treatment resistance. Currently, screening tests for GC are not cost-effective or have low accuracy. Previously, we described an extended phenotype of gastric cancer stem cells (GCSCs; CD24⁺CD44⁺CD54⁺EpCAM⁺) that is associated with metastasis and tumor stage in GC patients. The goal of the current research is to evaluate the presence of these GCSCs in the peripheral blood of GC patients and healthy volunteers. A total of 73 blood samples were collected from 32 GC patients and 41 healthy volunteers. After peripheral blood mononuclear cell (PBMC) extraction, multiparametric flow cytometry was performed looking for GCSCs. Using clustering data through artificial intelligence (AI), we defined high/low levels of circulating GCSCs (cGCSCs) and proceeded to evaluate its association with clinical and prognostic variables. Finally, a diagnostic test analysis was performed evaluating patients and healthy volunteers. We found that cGCSCs are present in most GC patients with a mean concentration of 0.48%. The AI clustering showed two groups with different cGCSC levels and clinical characteristics. Through statistical analysis, we confirmed the association between cGCSC levels and lymph node metastasis, distant metastasis, and overall survival. The diagnostic test analysis showed sensibility, specificity, and area under the curve (AUC) of 83%, 95%, and 0.911, respectively. Our results suggest that the assessment of cGCSCs CD24⁺CD44⁺CD54⁺EpCAM⁺ could be a potential noninvasive test, with prognostic value, as well as highly sensitive and specific for screening or diagnosis of GC; however, a larger scale study will be necessary to confirm this.