Blood cell origin of circulating microRNAs: a cautionary note for cancer biomarker studies.
Author(s): Pritchard CC, Kroh E, Wood B, Arroyo JD, Dougherty KJ, Miyaji MM, Tait JF, Tewari M
Publication: Cancer Prev Res (Phila), 2012, Vol. 5, Page 492-7
PubMed ID: 22158052 PubMed Review Paper? No
Purpose of Paper
The purpose of this paper was to determine if plasma levels of circulating microRNAs (miRNAs) reported in the literature to be tumor biomarkers are reflective of blood cell counts.
Conclusion of Paper
46 of the 79 miRNA species previously reported in the literature to be solid tumor biomarkers were highly expressed in at least one blood cell type from a healthy individual. Plasma miRNA expression reflected the blood cell composition of the sample, as plasma levels of miRNA species that exhibited a high level of expression in lymphoid or myeloid cells were correlated with lymphoid and myloid cell counts, respectively, in 43 K2EDTA plasma specimens. Further, levels of miRNA highly expressed in red blood cells were enriched 20-30 fold in plasma when the specimen was hemolyzed. Plasma levels of miRNAs highly expressed in myeloid cells and lymphoid cells shadowed changes in myeloid cell and lymphoid cell counts, respectively, in a patient undergoing myloablative chemotherapy and hematopoetic stem cell transplant.
Studies
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Study Purpose
The purpose of this study was to determine if plasma levels of circulating miRNAs reported in the literature to be tumor biomarkers are reflective of blood cell counts. Blood from a single healthy patient was separated into cellular components and K2EDTA plasma. K2EDTA plasma and complete blood count results were obtained from 42 consecutive patients with a wide range of diagnoses. Further plasma specimens were obtained from a single patient over the course of myloablative chemotherapy. miRNA was isolated on the day of plasma collection and was quantified using individual and array real-time qRT-PCR.
Summary of Findings:
46 of the 79 miRNA species previously reported in the literature to be solid tumor biomarkers were highly expressed in at least one blood cell type from a healthy individual. The plasma miRNA expression profile was reflective of the blood cell population, as 42 of the 46 miRNAs that were highly expressed in blood cells were also highly expressed in plasma. Specifically, plasma levels of 4 miRNAs (which were highly expressed in myeloid cells) were correlated with myeloid cell counts in 42 K2EDTA plasma specimens. Plasma levels of an additional miRNA that was highly expressed in lymphoid cells was modestly correlated (r=0.67) with lymphocyte counts, but plasma levels of a liver-specific miRNA were not correlated with any blood cell count. Similarly, levels of 4 miRNA highly expressed in red blood cells were enriched 20-30 fold in plasma when the specimen was hemolyzed, but similar changes in levels of non-red blood cell miRNA were not found after hemolysis. Plasma levels of miRNAs highly expressed in myeloid cells and lymphoid cells mirrored changes in myeloid cell and lymphoid cell counts, respectively, in a patient undergoing myloablative chemotherapy and hematopoetic stem cell transplant.
Biospecimens
Preservative Types
- None (Fresh)
Diagnoses:
- Normal
- Neoplastic - Lymphoma
- Neoplastic - Carcinoma
- Other diagnoses
- Neoplastic - Other
- Cardiovascular Disease
- Neoplastic - Leukemia
Platform:
Analyte Technology Platform RNA Low density array Cell count/volume Hematology/ auto analyzer Cell count/volume Flow cytometry RNA Real-time qRT-PCR Pre-analytical Factors:
Classification Pre-analytical Factor Value(s) Biospecimen Aliquots and Components Blood and blood products Whole blood
Plasma
Preaquisition Biomarker level A range of complete blood counts
Biospecimen Aliquots and Components Hemolysis Absent
Present
Biospecimen Acquisition Time of biospecimen collection 5 days pre-infusion
4 days pre-infusion
3 days pre-infusion
1 days pre-infusion
Infusion of hematopoetic stem cell
1 day post-infusion
3 day post-infusion
5 days post-infusion
7 days post-infusion
9 days post-infusion
11 days post-infusion
13 days post-infusion
15 days post-infusion
27 days post-infusion