Blood biomarkers may help to identify aggressive inflammatory breast cancer

Researchers have identified RNA signatures in blood that may distinguish inflammatory breast cancer from other breast cancer subtypes

Inflammatory breast cancer is one of the most aggressive forms of breast cancer, yet conventional genomic analysis has struggled to separate it clearly from non-inflammatory breast cancers because many cancer-related gene mutations appear similar across subtypes. This has limited the development of reliable diagnostic markers and has made it more difficult to monitor disease progression without tumour tissue samples taken as biopsies in the clinic.

Researchers at The University of Texas MD Anderson Cancer Center, Houston, Texas, USA and The University of Texas at Austin have now reported that specific RNA signatures present in blood, peripheral blood cells, plasma as well as in tumour samples can distinguish between inflammatory and non-inflammatory breast cancer, and from healthy samples.

The team used a more advanced form of RNA sequencing that employs a thermostable group II intron reverse transcriptase (TGIRT) enzyme capable of capturing a broader range of complex and fragmented RNA molecules than conventional sequencing methods. The method uses a robust enzyme that can capture a broader range of RNA types than standard RNA-sequencing approaches, including complex, fragmented and non-coding RNA molecules that may otherwise be missed.

“These findings provide novel insights into inflammatory breast cancer that should enable clinicians to monitor disease progression simply through liquid biopsy,” said Dr. Savitri Krishnamurthy, professor of anatomic pathology at Anderson.

“Because it is so difficult to obtain tumour samples, these blood-based biomarkers could be truly transformative in developing treatments for this patient population,” she said.

The research was led by Krishnamurthy in collaboration with Dr. Alan Lambowitz at The University of Texas at Austin and Dr. Naoto Ueno at the University of Hawai‘i Cancer Center. By using TGIRT sequencing, the researchers were able to analyse protein-coding genes associated with inflammatory breast cancer tumours and to identify RNA patterns that differed from those seen in non-inflammatory breast cancer.

Blood samples from patients with inflammatory breast cancer showed high levels of non-coding RNA and higher levels of white blood cells than samples from healthy individuals or patients with non-inflammatory breast cancer. The researchers said this pattern suggested immune activation and possible disruption of RNA splicing, the cellular process that removes non-coding sections from RNA before mature messenger RNA is produced.

In plasma samples, the genes most strongly represented in inflammatory breast cancer were linked to intron RNA fragments. Introns are non-coding regions within genes that are usually removed during RNA splicing. By contrast, healthy blood samples mainly contained messenger RNA fragments, which are shorter degraded pieces of RNA involved in the regulation of gene activity.

The findings point to several potential blood-based biomarkers that could support earlier diagnosis, improve disease monitoring and help researchers to develop therapies that reflect the biological features of inflammatory breast cancer. The work may be particularly important because inflammatory breast cancer can progress rapidly and tumour samples can be difficult to obtain.

For further reading please visit: 10.1126/sciadv.adu0031