Organ-selective miRNAs as circulating biomarkers for cancer detection

The biology of circulating microRNA (miRNA) is of major clinical interest due to a need for practical liquid biopsy strategies for early detection or guiding clinical-decision making. Although cell-free miRNAs can inform on the presence of cancerous lesions, their association with affected tissues is often unclear. In this study, we sought to identify organ and tumor-selective miRNAs and evaluated their release or absence in extracellular vesicle (EV) plasma fractions of healthy individuals and patients with cancer. With comparative analysis of miRNA expression across 48 cancer types (n=9781) we identified 324 tissue-enriched and 96 tissue-specific microRNAs. The candidates were validated in an independent cohort of cancer biopsies and compared to expression in healthy tissues (n=2460), providing the most extensive catalog of organ-selective miRNAs to date. Strongly organ-selective miRNAs are expressed primarily in the brain, ovaries, testis, prostate, adrenal glands and lymph node tissues. To determine the contribution of individual organs to circulating miRNA pool, we sequenced the miRNome of plasma EVs from healthy individuals (n=20) and built permeability scores which estimate the abundance of organ-selective miRNAs in plasma EVs. Merging the expression levels of prostate-selective miRNAs in plasma EVs into a 5-miRNA prostate-signature, we could readily distinguish prostate cancer from healthy controls (AUC=0.84,n=45). Accordingly, the prostate-miRNA signature does not distinguish colon- and head&neck cancer from the controls.We propose that incorporating tissue origin of circulating miRNAs in biomarker panels can improve reliability of circulating miRNA signatures for defined cancer types.