cfRNA

✅ or ✨ : recommended readings

cfRNA (cell-free RNA) is also called exRNA (extracellular RNA)

See cfRNA Analysis for the Analysis Methods.
See cfRNA-seq Tech. for the Sequencing Methods.

I. Representative cfRNA Studies

DETECTOR-seq method:

✅ 2024 Clinical and Translational Med - Depletion-assisted multiplexed cell-free RNA sequencing reveals distinct human and microbial signatures in plasma versus extracellular vesicles

Targeted RNA-seq strategy:

✅2025 Nature - An ultrasensitive method for detection of cell-free RNA
2025 Nature Med - Clinical utility of targeted RNA sequencing in cancer molecular diagnostics
2022 Nature - Early prediction of preeclampsia in pregnancy with cell-free RNA
2022 Nature - RNA profiles reveal signatures of future health and disease in pregnancy

Add TE-RNA:

✅2023 Nature BME - Nature Profiling of repetitive RNA sequences in the blood plasma of patients with cancer

Add microbial RNA:

✅2025 Nature Biotechnology - Modifications of microbiome-derived cell-free RNA in plasma discriminates colorectal cancer samples
✅2022 eLife - Cancer type classification using plasma cell-free RNAs derived from human and microbes

Add Fragmented RNA:

✅2025 Genome Biology - Peak analysis of cell-free RNA finds recurrently protected narrow regions with clinical potential

Combine with other cfOmics:

✅ 2023 Cell Rep Med. - Cell-free multi-omics analysis reveals potential biomarkers in gastrointestinal cancer patients’ blood

Mechanism study of candidate RNA:

2018 Nature Med. - Cancer cells exploit an orphan RNA to drive metastatic progression

II. cfRNA Studies

Cancer

Long

✅ Targeted long cfRNA-seq: 2025 Nature - An ultrasensitive method for detection of cell-free RNA
✅2025 Nature Med - Clinical utility of targeted RNA sequencing in cancer molecular diagnostics
✅2025 Nature Biotechnology - Modifications of microbiome-derived cell-free RNA in plasma discriminates colorectal cancer samples
✅ cfDNA+cfDNAmet+cfRNA-S+cfRNA-L - 2023 Cell Reports Medicine - Cell-free multi-omics analysis reveals potential biomarkers in gastrointestinal cancer patients’ blood
2023 Nature biomedical engineering - Nature Profiling of repetitive RNA sequences in the blood plasma of patients with cancer
2023 Nature Commn. - Terminal modiﬁcations independent cell-free RNA sequencing enables sensitive early cancer detection and classiﬁcation
2022 NPJ precision oncology - Plasma cell-free RNA proﬁling distinguishes cancers from premalignant conditions in solid and hematologic malignancies
2021 Clinical Chem. - Single Cell and Plasma RNA Sequencing for RNA Liquid Biopsy for Hepatocellular Carcinoma
long cfRNA-mRNA: 2021 Nature Commn. - Grail - A comprehensive characterization of the cell-free transcriptome reveals tissue- and subtype-specific biomarkers for cancer detection
long evRNA-mRNA: 2021 Mol Cancer - Circulating exosomal mRNA profiling identifies novel signatures for the detection of prostate cancer
long cfRNA-ncRNA - 2021 Theranostics - Integrative analysis of long extracellular RNAs reveals a detection panel of noncoding RNAs for liver cancer
✨ long evRNA-seq: 2020 GUT Plasma extracellular vesicle long RNA profiling identifies a diagnostic signature for the detection of pancreatic ductal adenocarcinoma
mRNA/lncRNA fragments: 2019 EMBO J. - Phospho‐RNA‐seq: a modified small RNA‐seq method that reveals circulating mRNA and lncRNA fragments as potential biomarkers in human plasma
SILVER-seq: 2019 PNAS - Extracellular RNA in a single droplet of human serum reflects physiologic and disease states
long evRNA-seq: 2019 Clinical Chemistry - Extracellular Vesicles Long RNA Sequencing Reveals Abundant mRNA, circRNA, and lncRNA in Human Blood as Potential Biomarkers for Cancer Diagnosis
exoRBase: 2018 NAR - exoRBase: a database of circRNA, lncRNA and mRNA in human blood exosomes
2018 PNAS - Human plasma and serum extracellular small RNA reference profiles and their clinical utility
exRNA Components: 2017 Nature Communication - Coding and noncoding landscape of extracellular RNA
Prospective Review: 2017 Noncoding RNA - RNA Biomarkers: Frontier of Precision Medicine for Cancer

Long - Platelet

✅ Platelet RNA: 2022 Cancer Cell - Detection and localization of early- and late-stage cancers using platelet RNA
2022 Genome Medicine - RNA profiling of blood platelets noninvasively differentiates colorectal cancer from healthy donors and noncancerous intestinal diseases: a retrospective cohort study
Platelet RNA: 2015 Cancer Cell - RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics
Platelet RNA: 2017 Cancer Cell - Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets

Small/Frag.

✅2025Genome Biology - Peak analysis of cell-free RNA finds recurrently protected narrow regions with clinical potential
✨ oncRNA: 2024 bioRxiv - Systematic annotation of orphan RNAs reveals blood-accessible molecular barcodes of cancer identity and cancer-emergent oncogenic drivers
unannotated exRNAs: 2021 GUT - Unannotated small RNA clusters associated with circulating extracellular vesicles detect early stage liver cancer
small exosomal RNA: 2019 Molecular Cancer - Exosomal tRNA-derived small RNA as a promising biomarker for cancer diagnosis
small cfRNA: 2015 Scientific Report - Plasma extracellular RNA profiles in healthy and cancer patients
structured ncRNA domain (small cfRNA-seq): 2019 Clinical chemistry - Noncoding RNAs serve as diagnosis and prognosis biomarkers for hepatocellular carcinoma
✨ oncRNA: 2018 Nature Med. - Cancer cells exploit an orphan RNA to drive metastatic progression
miRNA7: 2011 JCO - Jia Fan - Plasma MicroRNA Panel to Diagnose Hepatitis B Virus–Related Hepatocellular Carcinoma

Pregnancy

(ccfDNA - 2023 Lancet Cell-free fetal DNA for genetic evaluation in Copenhagen Pregnancy Loss Study (COPL): a prospective cohort study)
✅ long cfRNA-seq: 2022 Nature Early prediction of preeclampsia in pregnancy with cell-free RNA
Captured long cfRNA-seq: 2022 Nature RNA profiles reveal signatures of future health and disease in pregnancy
2020 Science translational medicine - Circulating transcripts in maternal blood reflect a molecular signature of early-onset preeclampsia
✅ Long cfRNA-seq: 2018 Science - Noninvasive blood tests for fetal development predict gestational age and preterm delivery
long cfRNA-seq: 2017 Clinical chemistry - Simultaneously Monitoring Immune Response and Microbial Infections during Pregnancy through Plasma cfRNA Sequencing

Infectious Diseases

2024 Nature Communications - Circulating cell-free RNA in blood as a host response biomarker for detection of tuberculosis
2022 Genome Res. - Plasma cell-free RNA characteristics in COVID-19 patients

Neural Diseases

small cfRNA - 2021 PNAS - - Small noncoding RNA profiling across cellular and biofluid compartments and their implications for multiple sclerosis immunopathology
long cfRNA-mRNA: 2020 Science Advance - Noninvasive characterization of Alzheimer’s disease by circulating cell-free messenger RNA next-generation sequencing
cfRNA: 2020 Current Biology - Presymptomatic increase of an extracellular RNA in blood plasma is associated with the development of Alzheimer’s disease

ERCC (2019 Cell papers)

Collections of exRNA Consortium (ERCC) @ Cell

Outlook collection of Nature (Could tracking RNA in body fluids reveal disease? )

exceRpt: Cell system 2019 - exceRpt: A Comprehensive Analytic Platform for Extracellular RNA Profiling
Extracellular carriers: Cell minireview 2019 - Mapping Extracellular RNA Sheds Lights on Distinct Carriers
ERCC perspective: Cell perspective 2019 - The Extracellular RNA Communication Consortium: Establishing Foundational Knowledge and Technologies for Extracellular RNA Research
Exosome preview: Cell preview 2019 - Explicating Exosomes: Reclassifying the Rising Stars of Intercellular Communication
✨ Exosome composition: Cell article 2019 - Reassessment of Exosome Composition
exRNA carriers: Cell resource 2019 - exRNA Atlas Analysis Reveals Distinct Extracellular RNA Cargo Types and Their Carriers Present across Human Biofluids
Small exRNA-seq: Cell resource 2019 - Small RNA Sequencing across Diverse Biofluids Identifies Optimal Methods for exRNA Isolation
Exosome PD-L1: Cell article 2019 - Suppression of Exosomal PD-L1 Induces Systemic Anti-tumor Immunity and Memory