Systematic annotation of orphan RNAs reveals blood-accessible molecular barcodes of cancer identity and cancer-emergent oncogenic drivers

TL;DR

This study identifies cancer-specific non-coding RNAs (oncRNAs) that can serve as molecular barcodes and potential biomarkers for cancer detection and monitoring.

Contribution

The study systematically annotates oncRNAs across 32 tumor types and demonstrates their utility as blood-accessible biomarkers and drivers of cancer progression.

Findings

OncRNA presence-absence patterns serve as molecular barcodes for cancer type and subtype identification.

Some oncRNAs drive cancer progression and are detectable in cell-free blood.

Circulating oncRNAs predict clinical outcomes in breast cancer patients.

Abstract

From extrachromosomal DNA to neo-peptides, reprogramming of cancer genomes leads to the emergence of cancer state-specific molecules. Here, we systematically identify and characterize a large repertoire of orphan non-coding RNAs (oncRNAs), a class of cancer-emergent small RNAs, across 32 tumor types. We show that oncRNA binary presence-absence patterns represent a digital molecular barcode that captures cancer type and subtype identities. Importantly, this barcode is partially accessible from the cell-free space as cancer cells secrete a subset of oncRNAs. Leveraging large-scale in vivo genetic screens in xenografted mice, we functionally identify driver oncRNAs in multiple tumor types. In a retrospective study across 192 breast cancer patients, we show that oncRNAs are reliably detected in blood and that changes in cell-free oncRNA burden predict both short-term and long-term clinical outcomes. Together, we establish that oncRNAs have potential roles in tumor progression and clinical utility in liquid biopsies for tumor-naive minimum residual disease monitoring.

•Systematic annotation of orphan non-coding RNAs (oncRNAs) across 32 cancers•OncRNAs patterns are molecular barcodes capable of distinguishing cancer types and subtypes•Using large-scale genetic screens, we find some oncRNAs drive cancer progression•Circulating oncRNAs are predictive of clinical outcomes in breast cancer patients

Systematic annotation of orphan non-coding RNAs (oncRNAs) across 32 cancers

OncRNAs patterns are molecular barcodes capable of distinguishing cancer types and subtypes

Using large-scale genetic screens, we find some oncRNAs drive cancer progression

Circulating oncRNAs are predictive of clinical outcomes in breast cancer patients

Wang et al. systematically annotate orphan non-coding RNAs (oncRNAs), cancer-emergent small RNAs, across 32 cancers. The study demonstrates that oncRNAs are informative of cancer types and have functional roles in cancer progression. Importantly, circulating oncRNAs are predictive of clinical outcomes in breast cancer patients, holding potential for liquid biopsy applications.

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