# Liquid RNA biopsy (cell-free, vesicle and platelet RNA)

Source: https://onco.cc/technologies/liquid-rna-biopsy/  
OnCo record `liquid-rna-biopsy` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Tests that read RNA from blood or urine, carried in tiny membrane packets, platelets or protein complexes, to find a cancer or read what its cells are doing.

## Summary

A tumour's RNA reaches blood and urine inside extracellular vesicles, bound to proteins, or taken up by platelets, and tests can read it there. Several urine tests are in routine use: ExoDx Prostate (three genes from urine vesicles), SelectMDx, MyProstateScore 2.0 and the Xpert Bladder Cancer Monitor, and Medicare's prostate biomarker policy lists the first three. In blood the field is younger: GRAIL's cell-free transcriptome study found that 68 per cent of 57,820 annotated genes are not detected in plasma from people without cancer, so tumour transcripts in those 'dark channels' stand out against a quiet background (Larson 2021); Exai Bio's orphan non-coding RNAs detected lung and colorectal cancer in validation sets (Karimzadeh 2024, Momen-Roknabadi 2025); and platelet RNA sequencing separated cancer from health in research cohorts (Best 2015).

The limits are measured. Naked RNA does not survive in plasma: more than 99 per cent of added free RNA could no longer be amplified after 15 seconds, while the body's own plasma RNA was stable for 24 hours in blood kept at 4 degrees (Tsui 2002), which is why what survives is packaged. Most of it comes from blood cells: 74 per cent (plus or minus 10) of circulating transcripts in people without cancer were from blood cells (Larson 2021, full text). No published study states a tumour fraction for cell-free RNA in parts per million, the unit residual disease DNA tests use, and no reference material for cell-free RNA assays was found.

## Fields

- Kind: Technology
- Status: emerging
- Last checked: 2026-11-04
- Also known as: cell-free RNA; cfRNA; circulating tumour RNA; ctRNA; exosomal RNA; extracellular vesicle RNA; urine RNA test; tumour-educated platelets
- Principle: RNA is extracted from plasma, urine, isolated vesicles or platelets, converted to DNA and measured by reverse-transcription PCR, targeted panels, microarrays or sequencing; a classifier turns the pattern into a score, or a tumour-specific transcript or fusion is called directly.
- Since: 2012
- Strengths: Reads which genes are switched on, including splice forms and fusions that DNA tests miss; Some tumour transcripts are absent from normal plasma, so background is low; Urine tests avoid a biopsy for the decision they inform
- Limitations: Free RNA is destroyed within seconds in plasma; only packaged RNA survives; Most plasma RNA comes from blood cells, so expression signals need tumour-specific genes; No parts-per-million tumour fraction or shared reference material for cell-free RNA; Blood tests for cancer detection are research or early commercial products

## Sources

- Larson et al., Nat Commun 2021: https://doi.org/10.1038/s41467-021-22444-1
- Tsui et al., Clin Chem 2002: https://doi.org/10.1093/clinchem/48.10.1647

## Connected records

- technologies: [Gene-expression prognostic assays](https://onco.cc/technologies/gene-expression-prognostic-assays/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [Multi-cancer early detection (MCED)](https://onco.cc/technologies/mced/), [Multitarget stool RNA test (ColoSense)](https://onco.cc/technologies/multitarget-stool-rna-test/), [RNA sequencing & expression profiling](https://onco.cc/technologies/rna-seq/), [Urine tests for bladder cancer (cytology, FISH, RNA and methylation)](https://onco.cc/technologies/urine-bladder-cancer-tests/)
- drugs: [ExoDx Prostate (IntelliScore)](https://onco.cc/drugs/exodx-prostate/), [miR Sentinel](https://onco.cc/drugs/mir-sentinel/), [MyProstateScore 2.0](https://onco.cc/drugs/myprostatescore-2/), [Progensa PCA3 Assay](https://onco.cc/drugs/progensa-pca3/), [SelectMDx](https://onco.cc/drugs/selectmdx/), [thromboSeq (tumour-educated platelet RNA)](https://onco.cc/drugs/thromboseq/), [Xpert Bladder Cancer Monitor](https://onco.cc/drugs/xpert-bladder-cancer-monitor/)
- cancers: [Bladder & urothelial cancer](https://onco.cc/cancers/urothelial/), [Breast cancer (all types)](https://onco.cc/cancers/breast-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Prostate cancer](https://onco.cc/cancers/prostate/)
- fronts: [Diagnostics & Biomarkers](https://onco.cc/fronts/diagnostics/), [Early Detection & Screening](https://onco.cc/fronts/early-detection/)
- key papers: [A comprehensive characterization of the cell-free transcriptome reveals tissue- and subtype-specific biomarkers for cancer detection](https://onco.cc/key-papers/paper-larson-cell-free-transcriptome-cancer-nat-commun-2021/), [A Novel Urine Exosome Gene Expression Assay to Predict High-grade Prostate Cancer at Initial Biopsy](https://onco.cc/key-papers/paper-mckiernan-urine-exosome-prostate-jama-oncol-2016/), [Cell types of origin of the cell-free transcriptome](https://onco.cc/key-papers/paper-vorperian-cell-types-cell-free-transcriptome-nat-biotechnol-2022/), [Deep generative AI models analyzing circulating orphan non-coding RNAs enable detection of early-stage lung cancer](https://onco.cc/key-papers/paper-karimzadeh-oncrna-lung-cancer-nat-commun-2024/), [Detection of AR-V7 in Liquid Biopsies of Castrate Resistant Prostate Cancer Patients: A Comparison of AR-V7 Analysis in Circulating Tumor Cells, Circulating Tumor RNA and Exosomes](https://onco.cc/key-papers/paper-nimir-ar-v7-ctc-ctrna-exosomes-cells-2019/), [Detection of Early-Stage Colorectal Cancer Using Cell-Free oncRNA Biomarkers and Artificial Intelligence](https://onco.cc/key-papers/paper-momen-roknabadi-oncrna-colorectal-clin-cancer-res-2025/), [Detection of High-grade Prostate Cancer Using a Urinary Molecular Biomarker-Based Risk Score](https://onco.cc/key-papers/paper-van-neste-urinary-biomarker-prostate-eur-urol-2016/), [Development and Validation of an 18-Gene Urine Test for High-Grade Prostate Cancer](https://onco.cc/key-papers/paper-tosoian-18-gene-urine-prostate-jama-oncol-2024/), [Expression of Small Noncoding RNAs in Urinary Exosomes Classifies Prostate Cancer into Indolent and Aggressive Disease](https://onco.cc/key-papers/paper-wang-urinary-exosome-small-rna-prostate-j-urol-2020/), [Improved EGFR mutation detection using combined exosomal RNA and circulating tumor DNA in NSCLC patient plasma](https://onco.cc/key-papers/paper-krug-exosomal-rna-ctdna-egfr-ann-oncol-2018/), [Longitudinal follow-up and performance validation of an mRNA-based urine test (Xpert Bladder Cancer Monitor) for surveillance in patients with non-muscle-invasive bladder cancer](https://onco.cc/key-papers/paper-cowan-xpert-bladder-monitor-bju-int-2021/), [Longitudinal Tracking of ALK-Rearranged NSCLC From Plasma Using Circulating Tumor RNA and Circulating Tumor DNA](https://onco.cc/key-papers/paper-heeke-alk-ctrna-ctdna-jto-clin-res-rep-2025/), [RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics](https://onco.cc/key-papers/paper-best-tumour-educated-platelets-cancer-cell-2015/), [Stability of endogenous and added RNA in blood specimens, serum, and plasma](https://onco.cc/key-papers/paper-tsui-plasma-rna-stability-clin-chem-2002/), [Systematic annotation of orphan RNAs reveals blood-accessible molecular barcodes of cancer identity and cancer-emergent oncogenic drivers](https://onco.cc/key-papers/paper-wang-orphan-rnas-breast-response-cell-rep-med-2026/), [The predictive and prognostic potential of plasma telomerase reverse transcriptase (TERT) RNA in rectal cancer patients](https://onco.cc/key-papers/paper-rampazzo-plasma-tert-rna-rectal-cancer-br-j-cancer-2018/), [Tumour extracellular vesicle surface Protein-mRNA integration assay for early detection of epithelial ovarian cancer](https://onco.cc/key-papers/paper-yen-ev-protein-mrna-ovarian-ebiomedicine-2025/), [Use of the Xpert Bladder Cancer Monitor Urinary Biomarker Test for Guiding Cystoscopy in High-grade Non-muscle-invasive Bladder Cancer: Results from the Randomized Controlled DaBlaCa-15 Trial](https://onco.cc/key-papers/paper-dreyer-xpert-bladder-dablaca-15-eur-urol-2025/)
- bottlenecks: [Naming which clone or phenotype is left after treatment](https://onco.cc/bottlenecks/b-subclone-attribution-residual-disease/)
- ideas: [Detect tumours changing cell type from RNA in the blood](https://onco.cc/ideas/idea-bio1-cfrna-plasticity-tracking/), [Read tumour RNA and tumour DNA from the same blood draw to find and type residual cancer](https://onco.cc/ideas/idea-stack-ctdna-and-tumour-rna-residual-disease/)
- companies: [Exai Bio](https://onco.cc/companies/exai-bio/)

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