Identification of circulating myeloid cells as a potential diagnosis and recurrence marker of pancreatic ductal adenocarcinoma through the single-cell analysis

Abstract

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive malignancy with a poor survival rate, largely due to the lack of biomarker for early detection. Given the crucial roles of circulating and tumor-infiltrating myeloid cells in PDAC progression, the identification of specific subsets of them can be a biomarker in liquid biopsies for diagnosis and prediction of recurrence risk of PDAC. Methods: We analyzed PDAC tissue microarray by immunohistochemistry to measure cytokine expressions. Peripheral blood cells of PDAC patients were subjected to define distinct cell population of PDAC patients by single-cell RNA sequencing and flow cytometry. In addition, the presence of myeloid cells was analyzed by murine xenograft/orthotropic models of PDAC cell lines. Finally, we performed a clinical study to evaluate the correlation of IL-10R2 expression and PDAC diagnosis or recurrence. Results: We found enriched IL-10R2+/IL-22R1 + myeloid cells in peripheral blood from PDAC patients, and that they display a signature association with tumor-educated monocytes. In addition, we verified the positive correlation of pancreatic tumor growth with increased IL-10R2+/IL-22R1 + myeloid cells through the murine xenograft/orthotropic models. Most importantly, the IL-10R2 + myeloid cells signaled tumor recurrence 130 days faster than CA19-9 in post-pancreatectomy patients. Conclusions: Enriched IL-10R2 + myeloid cells in PDAC patient’s blood may benefit uncomplicated and effective diagnostic marker and indicator of recurrence.