Distinctive RNA fragments circulating in blood plasma may help identify inflammatory breast cancer (IBC) and monitor disease progression through minimally invasive liquid biopsy testing, according to new research published in Science Advances.
IBC is a rare but highly aggressive form of breast cancer that accounts for a disproportionate number of breast cancer deaths. Diagnosis currently relies mainly on clinical signs because genomic sequencing has not revealed consistent mutations that clearly distinguish IBC from other breast cancers. Tumor sampling is also challenging because IBC often grows as scattered clusters rather than forming a discrete mass.
Researchers from the University of Texas at Austin and MD Anderson Cancer Center used an advanced RNA sequencing method called TGIRT-seq to analyze tumor tissue, peripheral blood mononuclear cells, and plasma samples from patients with IBC, patients with non-IBC breast cancer, and healthy donors. The technique enabled broad profiling of coding and noncoding RNAs, including RNA species that are often missed by conventional sequencing approaches.
The study found widespread abnormalities in RNA transcription and splicing in IBC samples. Unlike plasma from patients with non-IBC disease, plasma from patients with IBC contained large amounts of intron-derived RNA fragments – partially processed RNA molecules associated with disrupted gene regulation. These plasma RNA patterns mirrored changes seen in tumor tissue and immune cells, suggesting that blood-based RNA profiling may provide a real-time view of tumor biology.
Several potential biomarker candidates emerged from the analysis. One RNA fragment derived from the TRBJ1-6 gene was detected in all 10 IBC plasma samples but was absent from healthy donor and non-IBC plasma samples. The investigators suggested that this marker may reflect disease-specific immune activity and could support future diagnostic assay development.
The researchers also identified multiple noncoding RNAs, microRNAs, and inflammatory-response genes associated with IBC biology. Many were linked to pathways involved in inflammation, hypoxia, coagulation, and epithelial-to-mesenchymal transition, processes already implicated in aggressive tumor behavior.
The findings highlight the growing potential of RNA-based liquid biopsy testing beyond mutation analysis alone. Because plasma RNA may change rapidly during disease progression or treatment, the approach could eventually support earlier diagnosis, therapy monitoring, and relapse detection in patients with IBC.
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