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MicroRNA Signature May Help Provide Glioblastoma Patient Prognosis

NEW YORK (GenomeWeb) – A four-microRNA signature may help provide a prognosis in glioblastoma patients and sway treatment decisions, according to a team of German researchers.

The Helmholtz Zentrum München- and University of Munich-led team examined formalin-fixed paraffin embedded samples and survival data from 36 glioblastoma patients to uncover the signature, and found that it could distinguish high- and low-risk glioblastoma patients, as the group reported recently in the journal Oncotarget.

"We repeatedly detected four miRNAs in tumors that had a particularly poor prognosis," first author Karim-Maximilian Niyazi from the University of Munich's Grosshadern Hospital said in a statement.

The genes thought to be regulated by these four miRNAs are involved in a number of tumorigenesis-linked activities like immune response, extracellular matrix organization, and more. Such a signature, Niyazi and his colleagues noted, could be used to stratify patients and identify those who might benefit from more intensive treatment.

Glioblastomas, they noted, are the most common brain tumors in adults, though they are aggressive tumors.

Niyazi and his colleagues analyzed miRNA expression profiles in FFPE samples obtained from 36 patients who'd undergone adjuvant radiochemotherapy and for whom outcomes data were available. Based on their miRNA expression microarray data, the researchers linked four miRNAs — hsa-let-7a-5p, hsa-let- 7b-5p, hsa-miR-125a-5p and hsa-miR-615-5p — to overall survival.

They then developed a risk score that placed patients into either a high- or a low-risk group. Patients in the high-risk group had a median survival of 13.5 months, while patients in the low-risk group had a median survival of 18.4 months, the researchers reported.

Individually, each of these four miRNAs could predict overall survival, the researchers added. The expression of the miRNAs hsa-let-7a-5p, hsa-let-7b-5p, and hsa-miR-125a-5p were positively correlated with overall survival, but that of hsa-miR-615-5p was negatively correlated with overall survival.

Niyazi and his colleagues validated the prognostic value of their miRNA signature in an age- and sex-matched cohort of glioblastoma patients from The Cancer Genome Atlas who'd received the standard of care. They further technically validated their signature in a subset of samples using a qRT-PCR approach.

Two of the miRNAs in the signature belong to the let-7 family, which has a known tumor-suppression role in a number of cancers. Supporting that role, hsa-let-7a-5p and hsa-let-7b-5p had higher expression levels in the low-risk group as compared to the high-risk group, the researchers noted. In addition, hsa-miR-125a-5p was also recently reported to be a tumor suppressor in glioblastoma, and it too had higher expression levels in the low-risk group.

Through an miRNA-transcriptome correlation analysis, the researchers uncovered some 650 genes whose expression levels were associated with those of the four miRNAs. A pathway enrichment analysis uncovered more than two dozen statistically significant pathways, including the innate immune system, extracellular matrix organization, axon guidance, and a number of signaling pathways. Many of these pathways, Niyazi and his colleagues noted, have previously been linked to the development, progression, and migration of glioblastoma.

This signature could be used in the clinic to stratify glioblastoma patients, the researchers added. In their paper, they noted that their four-miRNA signature was robust on different platforms as the three datasets they relied upon had been analyzed using a Febit microarray, an Aglient microarray, and qRT-PCR.

"Our method could be used to identify candidates for alternative or intensified treatment options, as it is highly unlikely that patients with a high-risk score would benefit from standard therapy," senior author Kristian Unger from the Helmholtz Zentrum München said in a statement.

He and his colleagues have applied for a related patent.