Functional analysis of differential mRNAs in cancer peripheral blood: reflection of population shifts in myeloid-origin and lymphoid-origin cells

Functional enrichment analysis is usually adopted after the identification of differentially expressed (DE) genes in studies focusing on cancer peripheral blood (PB) gene expression. However, whether the disturbed functional signals reflect the expression changes in blood cells or the cell population shifts under cancer condition remains unclear. By deconvolving the gene expression profiles of multiple cancer datasets, we showed that the proportion of myeloid-origin cells increased whereas the proportion of lymphoid-origin cells decreased in cancer PB. The DE genes between cancer PB samples and controls were highly consistent with DE genes between myeloid-origin and lymphoidorigin cells, indicating that cell population shifts contributed predominantly to the differential signals in cancer PB. All of the functional categories enriched for cancer PB DE genes were enriched for DE genes between myeloid-origin and lymphoidorigin cells, suggesting that functional signals in cancer PB probably reflect the changes of population shifts in blood cells, thus the enriched functional categories might not be able to reflect the cell type specific expression changes. Therefore, caution should be taken in translational biomarker discovery based on human PB gene expression profiles.