Detection of Cancer with Serum miRNAs on an Oligonucleotide Microarray

Abstract

Micro RNAs (miRNAs) are a class of small, non-coding RNA species that play critical roles throughout cellular development and regulation. miRNA expression patterns taken from various tissue types often point to the cellular lineage of an individual tissue type, thereby being a more invariant hallmark of tissue type. Recent work has shown that these miRNA expression patterns can be used to classify tumor cells, and that this classification can be more accurate than the classification achieved by using messenger RNA gene expression patterns. One aspect of miRNA biogenesis that makes them particularly attractive as a biomarker is the fact that they are maintained in a protected state in serum and plasma, thus allowing the detection of miRNA expression patterns directly from serum. This study is focused on the evaluation of miRNA expression patterns in human serum for five types of human cancer, prostate, colon, ovarian, breast and lung, using a pan-human microRNA, high density microarray. This microarray platform enables the simultaneous analysis of all human microRNAs by either fluorescent or electrochemical signals, and can be easily redesigned to include newly identified miRNAs. We show that sufficient miRNAs are present in one milliliter of serum to detect miRNA expression patterns, without the need for amplification techniques. In addition, we are able to use these expression patterns to correctly discriminate between normal and cancer patient samples.

Discovery of circulating microRNAs associated with human prostate cancer using a mouse model of disease

“…13 Detectable levels of free miRNAs were recently found to exist in serum, 14 and subsequent studies have shown that circulating miRNAs can be useful markers of cancer. [15][16][17] In prostate cancer, the level of a number of miRNAs is altered in the serum of men with advanced disease and these markers can be used to discriminate cancer patients from healthy individuals. 11,[17][18][19] Moreover, two recent reports found that some circulating prostate cancer-associated miRNAs correlate with risk of disease progression 20 and other predictors of disease outcome, such as Gleason score and lymph-node status, 18 highlighting the prognostic potential of this class of molecules.…”

“…[15][16][17] In prostate cancer, the level of a number of miRNAs is altered in the serum of men with advanced disease and these markers can be used to discriminate cancer patients from healthy individuals. 11,[17][18][19] Moreover, two recent reports found that some circulating prostate cancer-associated miRNAs correlate with risk of disease progression 20 and other predictors of disease outcome, such as Gleason score and lymph-node status, 18 highlighting the prognostic potential of this class of molecules. However, the clinical utility of these miRNAs is yet to be validated in larger cohorts, and more comprehensive analyses to identify other circulating miRNAs associated with prostate cancer are needed.…”

Exosomal microRNAs in liquid biopsies: future biomarkers for prostate cancer

“…MiRNAs have identified deregulated in plasma and serum microvesicles in prostate cancer patients compared with healthy control [64] and were also associated with the stage of the disease, the Gleason score and lymph node metastasis. For instance, Lodes et al found 15 miRNAs (miR-16, -92a, -103, -107, -197, -34b, -328, -485-3p, -486-5p, -92b, -574-3p, -636, -640, -766, -885-5p) overexpressed in serum from stage 3 and 4 prostate cancer patients compared with healthy controls [65]. Furthermore, Mahn et al, found miR-26a, miR-195, and let-7i to be up-regulated in patients with prostate cancer compared with patients affected by benign prostatic hyperplasia [66].…”

Circulating microRNAs: macro-utility as markers of prostate cancer?

“…Moreover, miR-141 was correlated with serum PSA levels and could detect individuals with advanced PCa with 60% sensitivity at 100% specificity. A subsequent study used a custom microarray to profile miRNAs in serum from patients with various cancer types and identified 15 miRNAs at elevated levels in the circulation of PCa patients (Lodes et al 2009). However, only six PCa samples from men with significant disparities, including age, disease grades, and modes of treatment, were analyzed.…”