Identification of human peripheral blood monocyte gene markers for early screening of solid tumors

PLoS One. 2020 Mar 30;15(3):e0230905. doi: 10.1371/journal.pone.0230905. eCollection 2020.

Abstract

As cancer mortality is high in most regions of the world, early screening of cancer has become increasingly important. Minimally invasive screening programs that use peripheral blood mononuclear cells (PBMCs) are a new and reliable strategy that can achieve early detection of tumors by identifying marker genes. From 797 datasets, four (GSE12771, GSE24536, GSE27562, and GSE42834) including 428 samples, 236 solid tumor cases, and 192 healthy controls were chosen according to the inclusion criteria. A total of 285 genes from among 440 reported genes were selected by meta-analysis. Among them, 4 of the top significantly differentially expressed genes (ANXA1, IFI44, IFI44L, and OAS1) were identified as marker genes of PBMCs. Pathway enrichment analysis identified, two significant pathways, the 'primary immunodeficiency' pathway and the 'cytokine-cytokine receptor interaction' pathway. Protein- protein interaction (PPI) network analysis revealed the top 27 hubs with a degree centrality greater than 23 to be hub genes. We also identified 3 modules in Molecular Complex Detection (MCODE) analysis: Cluster 1 (related to ANXA1), Cluster 2 (related to IFI44 and IFI44L) and Cluster 3 (related to OAS1). Among the 4 marker genes, IFI44, IFI44L, and OAS1 are potential diagnostic biomarkers, even though their results were not as remarkable as those for ANXA1 in our study. ANXA1 is involved in the immunosuppressive mechanism in tumor-bearing hosts and may be used in a new strategy involving the use of the host's own immunity to achieve tumor suppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Early Detection of Cancer*
  • Gene Regulatory Networks
  • Genetic Markers / genetics*
  • Humans
  • Molecular Sequence Annotation
  • Monocytes / metabolism*
  • Neoplasms / blood
  • Neoplasms / diagnosis*
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Protein Interaction Mapping

Substances

  • Genetic Markers

Grants and funding

This work was supported by National Natural Science Foundation of China [grant number 81660041 to L.D.]; Natural Science Foundation of Jiangxi Province [grant numbers 20171BAB205109 to X.T., 20181BAB205008 to L.D.]; Youth Science Foundation of Jiangxi Province [grant number 20161BAB215248 to Y.X.]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.