Integrating contextual miRNA and protein signatures for diagnostic and treatment decisions in cancer

Abstract

The promise of personalized medicine is highly dependent on the identification of biomarkers that inform diagnostic decisions and treatment options, as well as on the accurate, rapid and cost-effective detection and interpretation of these biomarkers. miRNAs, which are short noncoding regulatory RNAs, are rapidly emerging as a novel class of biomarkers with a unique set of biological and chemical properties that makes them very appealing candidates for theranostic applications in cancer. Since the utility of some protein-encoding gene biomarkers is already exploited in routine clinical practice, it will be important to identify areas in which miRNAs provide complementary or superior information to these existing (and other translational) biomarkers to enhance the diagnostic, prognostic and predictive power of molecular characterization of tumors. In this article, the challenges and opportunities for integration of miRNA-based assays in the clinical toolkit to improve care and management of patients afflicted with solid tumors will be discussed.

miR-101 inhibits cell proliferation by targeting Rac1 in papillary thyroid carcinoma

“…Accumulated evidence have identified miRNAs that aid in the diagnosis of disease and serve as potential targets for therapy in the future (25). Recent successful preclinical therapeutic trials in cancers include miR-380-5p replacement in neuroblastoma (26) and miR replacement/anti-miR combination therapy in hepatoblastoma (27).…”

Modulation of Cancer Progression by Tumor Microenvironmental Leukocyte-Expressed microRNAs

“…Altered miRNA expression has been reported in all studied solid tumors, including breast, brain, colorectal, gastric, lung, ovarian, pancreatic, prostate, skin, and thyroid cancers (Barbarotto et al, 2008;Fabbri, 2010;Li et al, 2010;Liu et al, 2011;Pallante et al, 2010;Sempere, 2011). Carcinomas of the breast, colon and lung collectively account for more than 247,000 cancer-related deaths per year in the United States (Jemal et al, 2010).…”

“…We and others have implemented similar in situ hybridization (ISH) methods to identify the cellular compartment(s) of altered miRNA expression in a variety of solid tumors, including brain, breast, colorectal, lung, pancreatic, and prostate cancer (Dillhoff et al, 2008;Donnem et al, 2011;Gupta & Mo, 2011;Habbe et al, 2009;Jorgensen et al, 2010;Liu et al, 2010a;Nelson et al, 2006Nelson et al, , 2010Nelson & Wilfred, 2009;Nielsen et al, 2011;Preis et al, 2011;Qian et al, 2011;Rask et al, 2011;Schepeler et al, 2008;Schneider et al, 2011;Sempere et al, 2007Sempere et al, , 2010Yamamichi et al, 2009). miR-21 and miR-155 are frequently detected at higher levels in solid tumors and their differential expression correlates with outcome (Barbarotto et al, 2008;Sempere, 2011). Using a combined ISH/IHC multiplex assay, we determined that miR-21 and miR-155 are expressed in different cellular compartments of the TME (Sempere et al, 2010).…”

“…A particular active area of research has been high-throughput expression profiling of miRNAs in a variety of cancer types (Barbarotto et al, 2008;Sempere, 2011). The general interpretation of these expression profiling experiments has been to assign altered miRNA expression to the cancer cells and promptly labelled the implicated miRNA as having tumor suppressive or oncogenic properties depending on whether miRNA levels were detected a lower or higher levels, respectively, in tumor tissues compared to normal.…”

“…The general interpretation of these expression profiling experiments has been to assign altered miRNA expression to the cancer cells and promptly labelled the implicated miRNA as having tumor suppressive or oncogenic properties depending on whether miRNA levels were detected a lower or higher levels, respectively, in tumor tissues compared to normal. However, the cancer cell compartment of many of the most aggressive types of solid tumors represents a minority of the variety of cell types in cancer lesions (Sempere, 2011). A tumor microenvironmental (TME) cell type invariably associated with cancer progression is the leukocyte.…”