Researchers at the University of Texas MD Anderson Cancer Center and the University of Texas at Austin have identified specific blood-based genomic biomarkers that distinguish inflammatory breast cancer from other subtypes, providing a new, less invasive method for early diagnosis, disease progression monitoring, and treatment development for patients with this aggressive disease.
This study scientific progressused an improved method of RNA sequencing called TGIRT sequencing. This provides a more comprehensive overview of all RNA types and amounts present in a given sample. The study was led by Savitri Krishnamurthy, MD, professor of anatomic pathology at UT MD Anderson, in collaboration with Alan Lambowitz, MD, of UT Austin and Naoto Ueno, MD, of the University of Hawaii Cancer Center.
These findings should provide new insights into inflammatory breast cancer and allow clinicians to easily monitor disease progression through liquid biopsies. As tumor samples are very difficult to obtain, these blood-based biomarkers have the potential to be a real game-changer in the development of treatments for this patient population. ”
Savitri Krishnamurthy, MD, Professor of Anatomical Pathology, UT MD Anderson University
Why is it so difficult to identify biomarkers for IBC, and what have researchers done differently?
Although IBC is considered the most lethal and aggressive type of breast cancer, most genomic sequencing techniques have not been able to differentiate IBC from non-inflammatory breast cancer because cancer-associated genetic mutations are very similar.
Additionally, standard RNA-seq methods use enzymes that struggle to process more complex RNA, resulting in a lot of information being skipped or missing in a given sample.
In this study, the researchers used a specialized sequencing method, TGIRT. It employs more powerful enzymes that can handle extreme environments, is more reliable, and can capture difficult and complex fragmented RNA.
What is the difference between IBC and other breast cancers?
TGIRT sequencing helped researchers develop a method to analyze various protein-coding genes unique to IBC tumors. They also found that blood samples from IBC patients contained higher levels of non-coding RNA and higher levels of white blood cells compared to blood samples from healthy or non-IBC patients. This suggests that the immune system is activated, resulting in RNA splicing imbalance and decreased mRNA production.
Similarly, in plasma samples, the genes overexpressed in IBC were intronic RNA fragments, non-coding parts within genes that are normally spliced out. However, healthy blood contains primarily mRNA fragments. mRNA fragments are shorter, degraded segments of messenger RNA that are normally degraded to control gene activity.
What does this mean for patients who may have IBC?
Overall, the researchers were able to identify several potential blood-based biomarkers for IBC in tumors, peripheral blood cells, and plasma, leading to the possibility of more effective methods for diagnosing and monitoring disease progression. These biomarkers will also aid in the development of new therapeutic strategies to address the unique features of this aggressive breast cancer subtype.
sauce:
University of Texas MD Anderson Cancer Center
Reference magazines:
Wiley, D. others. (2026). Widespread enhanced transcription in inflammatory breast cancer tumors and PBMCs affects RNA splicing and intronic RNAs in plasma. scientific progress. DOI: 10.1126/sciadv.adu0031. https://www.science.org/doi/10.1126/sciadv.adu0031
