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MicroRNAs Provide Prognostic Clues in Primary Central Nervous System Lymphoma

NEW YORK (GenomeWeb) – A team from Japan has tracked down a handful of microRNAs that appear to provide insights into patient outcomes in individuals with primary central nervous system lymphoma (PCNSL), a rare, aggressive form of B cell, nodal non-Hodgkin lymphoma.

As they reported online this week in PLOS One, the researchers used array-based miRNA profiling to narrow in on more than a dozen miRNAs that appeared to be linked to overall survival rates in more than two dozen individuals with PCNSL. They subsequently whittled that set down to three miRNAs with potential prognostic utility in PCNSL, including miRNAs linked to cell death, cell proliferation, and immune tolerance pathways.

"These results indicate that this miRNA signature is useful for prognostic prediction of PCNSL and would help us understand target pathways for therapies in PCNSL," corresponding author Ryuya Yamanaka, a cancer researcher at Kyoto Prefectural University of Medicine, and his colleagues wrote.

The team noted that prior studies have explored miRNAs in the blood or cerebrospinal fluid that might coincide with PCNSL or PCNSL patient outcomes. Even so, the authors noted that "to date, the comprehensive function, significance, and effectiveness of miRNAs as biomarkers in the clinical studies of PCNSL have not been elucidated."

With that in mind, the team used Affymetrix GeneChip arrays to assess miRNAs in tumor samples from 27 PCNSL patients between the ages of 31 and 76 years old, identifying 847 miRNAs.

When they searched for miRNAs with ties to PCNSL patient survival — which ranged from 188 to more than 3,600 days — the researchers narrowed in on 16 suspicious miRNAs expressed to some extent in all of the tumors. These miRNAs have been implicated in processes ranging from new blood vessel formation to cell migration, proliferation, and immune function, they noted, and were highly expressed in almost half the PCNSLs tested.

The team considered the prognostic clues provided by the 16-miRNA gene set, and by a subset of three quantitative PCR-validated miRNAs found by Random forest analysis and clustering analyses: miR-30d, miR-93, and miR-181b. Indeed, the expression profiles for miRNAs from both signatures could successfully separate PCNSL patients with poor or more favorable overall survival rates.

"Although the data is limited by the small sample size and there is less evidence for the above-mentioned function and signaling pathways at present, it would help us to better understand biological significances of the CNS signature of miRNAs in PCNSL," the authors concluded.