Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies

By Michael D. Mattie, Christopher C. Benz, Jessica Bowers, Kelly Sensinger, Linda Wong, Gary K. Scott, V. Fedele, David Ginzinger, R. Getts, Christopher M. Haqq. Molecular Cancer, 2006

703 citations recorded by the source corpus.

BackgroundRecent studies indicate that microRNAs (miRNAs) are mechanistically involved in the development of various human malignancies, suggesting that they represent a promising new class of cancer biomarkers. However, previously reported methods for measuring miRNA expression consume large amounts of tissue, prohibiting high-throughput miRNA profiling from typically small clinical samples such as excision or core needle biopsies of breast or prostate cancer. Here we describe a novel combination of linear amplification and labeling of miRNA for highly sensitive expression microarray profiling requiring only picogram quantities of purified microRNA.ResultsComparison of microarray and qRT-PCR measured miRNA levels from two different prostate cancer cell lines showed concordance between the two platforms (Pearson correlation R2 = 0.81); and extension of the amplification, labeling and microarray platform was successfully demonstrated using clinical core and excision biopsy samples from breast and prostate cancer patients. Unsupervised clustering analysis of the prostate biopsy microarrays separated advanced and metastatic prostate cancers from pooled normal prostatic samples and from a non-malignant precursor lesion. Unsupervised clustering of the breast cancer microarrays significantly distinguished ErbB2-positive/ER-negative, ErbB2-positive/ER-positive, and ErbB2-negative/ER-positive breast cancer phenotypes (Fisher exact test, p = 0.03); as well, supervised analysis of these microarray profiles identified distinct miRNA subsets distinguishing ErbB2-positive from ErbB2-negative and ER-positive from ER-negative breast cancers, independent of other clinically important parameters (patient age; tumor size, node status and proliferation index).ConclusionIn sum, these findings demonstrate that optimized high-throughput microRNA expression profiling offers novel biomarker identification from typically small clinical samples such as breast and prostate cancer biopsies.

Subfields: Cancer Research, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/e561b421c7b82794d96c3864246fbd16c97a96b9

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Citations in the corpus

Circulating microRNAs as Novel Minimally Invasive Biomarkers for Breast Cancer (2010, neutral): “The miRNA expression studies in breast cancer indicate their importance and potential use as disease classifiers and prognostic tools in this field.(8,9) A relevant and important feature of miRNAs is their remarkable stability.”
Normalization of microRNA expression levels in quantitative RT-PCR assays: identification of suitable reference RNA targets in normal and cancerous human solid tissues. (2008, neutral): “To date, only a handful of miRNA qRT-PCR studies have described some form of normalization, using RNA targets such as 5S (Takamizawa et al. 2004; Pineles et al. 2007), U6 (Choong et al. 2007; Corney et al. 2007; Shell et al. 2007), 18S (Iorio et al. 2007), or miR-16 or let-7a (Mattie et al. 2006).”
MicroRNA expression profiling in prostate cancer. (2007, positive): “... in the carcinoma samples are the same ones that have also been identified in at least one of the three previously published miRNA profiling studies, in which prostate carcinoma samples have been included: 33 of them were shown by Lu et al. (29) to be among the differentially expressed miRNAs tha”
MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype (2007, positive): “A third study found that a number of miRNAs were differentially expressed in breast tumor biopsies and that miRNA expression correlated with HER2 and estrogen receptor (ER) status [79].”
MicroRNA function in cancer: oncogene or a tumor suppressor? (2009, positive): “Mir-125a and miR-125b: Using microRNA expression profiling in breast cancer patients, both of these microRNAs were shown to be significantly downregulated in HER2- amplified and overexpressing breast cancers [71].”
Improved classification of breast cancer by analysis of genetic alterations and gene expression profiling (2011, neutral): “Follow-up studies have validated some of these miRNAs (40), suggested >30 miRNAs differentiating tumor subtypes (41, 42), and defined the cell-type-specific localization of a few of these miRNAs (43).”
Widespread deregulation of microRNA expression in human prostate cancer (2008, neutral): “In contrast, our protocol, and that of Lu et al. (2005) and Mattie et al. (2006) included purification of small RNAs, including mature miRNAs, before analysis, so precursor miRNAs would not be detected.”
A Pleiotropically Acting microRNA, miR-31, Inhibits Breast Cancer Metastasis (2009, positive): “Expression profiling of clinical breast tumors revealed reduced miR31 in luminal B (relative to luminal A), basal-like, and HER2+ tumors (Mattie et al., 2006; Blenkiron et al., 2007)—patterns of reduction that correlate with aggressive disease (Sørlie et al., 2001).”
Detection of elevated levels of tumour‐associated microRNAs in serum of patients with diffuse large B‐cell lymphoma (2008, positive): “…use of house-keeping microRNAs for qRT-PCR analysis, and because we could not detect U6 or 5s in sera samples, based on previously published results (Mattie et al, 2006; Zhang et al, 2006) and as recommended by the manufacturer (Applied Biosystems), we used MIRN16 (miR-16) levels for normalization.”
MicroRNAs: New Biomarkers for Diagnosis, Prognosis, Therapy Prediction and Therapeutic Tools for Breast Cancer (2015, positive): “In fact, the let-7 family is present in several miRNA expression signatures of BC tissues [183, 184] and also in other types of tumor [183, 185, 186].”