Diagnostic microRNA markers to screen for sporadic human colon cancer in blood.
We carried out this study to present proof-of-principal application, showing that by using a global microarray expression analysis, followed by quantitative stem-loop reverse transcriptase in conjunction with TaqMan® polymerase chain reaction (PCR) analysis of micro(mi)RNA genes, on limited number of plasma and tissue samples obtained from 20 individuals (five healthy, five TNM stage 0-1 colon cancer, five stage 2 and five stage 3), we were able to quantitatively monitor miRNA changes at the various TNM stages of colon cancer progression, particularly at the early, pre-malignant adenoma stage (e.g. polyps ≥ 1 cm with high grade dysplasia). The expression of some of the tested miRNAs showed less variability in tissue than in plasma. Nevertheless, our limited preliminary data on the plasma by itself show that plasma is well-suited for screening, and that the quantitative changes in the expression of a few cell-free circulatory mature miRNA molecules in plasma, that are associated with colon cancer progression, would provide for more sensitive and specific markers than those tests currently available on the market. In addition, analysis of miRNA molecules offers a quantitative and cost-effective non-invasive diagnostic approach for screening, than currently employed methods in a prevalent cancer that can be cured if it is detected at the early TNM stages, and that becomes deadly if not diagnosed before metastasis. Thus, a larger prospective and properly randomized clinical study using plasma derived from many control individuals and at various stages of colon cancer (TNM stages 0-IV) from patients, in order to corroborate the initial results, is now urgently needed in order to allow for a statistically valid analysis, standardizing test conditions which will provide a means for determining the true sensitivity and specificity of a miRNA-screening approach. This approach, when combined with bioinformatics analysis to correlate miRNA seed data with mRNA target data, would allow for a mechanistic understanding of how miRNAs regulate mRNA gene expression, and would offer a better comprehensive diagnostic screening test for early-detection of colon cancer non-invasively.
Department of Radiation Oncology, Leo W. Jenkins Cancer Center, The Brody School of Medicine at East Carolina University (ECU), Greenville, NC 27834, USA. gemtoxconsultants@yahoo.com
Farid E
FE
Ahmed
Nancy C
NC
Amed
Paul W
PW
Vos
Chris
C
Bonnerup
James N
JN
Atkins
Michelle
M
Casey
Gerard J
GJ
Nuovo
Wade
W
Naziri
John E
JE
Wiley
Ron R
RR
Allison
D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis / Q000473:pathology; D014408:Biomarkers, Tumor / Q000097:blood*; D003110:Colonic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000097:blood; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis
D014408:Biomarkers, Tumor; D035683:MicroRNAs