Population Change of Myeloid and Lymphoid Cells Contributes to the Blood-Based Protein Biomarkers

Abstract

Listen

Translate article

Background: It has been observed that myeloid cells proportion increases, while lymphoid cells proportion decreases in blood of both inflammatory and cancer patients, which explains the serum concentration changes of many protein biomarkers in cancer patients versus normal controls. Methods: From literature, cancer serum and/or plasm protein biomarkers were collected and their expression patterns were examined in the microarray data of myeloid and lymphoid cells. Serum from 30 pancreatic ductal adenocarcinoma (PDAC) patients, 30 pancreatitis patients and 30 healthy volunteers, was studied using the enzyme-linked immunosorbent assay (ELISA). Findings: Among 45 protein biomarkers for PDAC, the genes expressing 15 proteins were significantly dysregulated in myeloid cells versus lymphoid cells and 13 of them, except APOA2 and THBS1, were dysregulated to the same directions as in PDAC patients versus normal controls (binomial test, P = 3.7E-3). A further comparative study was carried out on other cancers and showed significantly consistency (binomial test, P = 1.54E-02). Experimentally, we confirmed that APOA2 and THBS1 were significantly up-regulated in PDAC patients versus normal controls (Student's t test, P < 0.05) as in myeloid cells versus lymphoid cells, while there were no significant differences between PDAC and pancreatitis patients. Interpretation: We demonstrate that the ratio shifts of myeloid and lymphoid cells might lead the observed changes of many secreted protein biomarkers for cancers. Funding Statement: National Natural Science Foundation of China, Natural Science Foundation of Fujian Province, Education and Scientific Research Projects of Young and Middle-aged Teachers in Fujian Province and Fujian Medical University. Declaration of Interests: All authors declare no conflict of interest. Ethics Approval Statement: All subjects gave their informed consent for inclusion before they participated in the study. The study was approved by the Ethics Committee of Fujian Medical University and all experiments were performed in accordance with the approved guidelines and regulations.