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Breast Cancer Survival Associated With Tumor Small Nucleolar RNA Profile, Study Finds

NEW YORK (GenomeWeb) – Canadian researchers have identified more than a dozen small nucleolar RNAs (snoRNAs) that appear to be associated with breast cancer survival.

As reported yesterday in PLOS One, the team used small RNA sequencing to assess snoRNAs in 104 breast cancers and 11 normal breast tissue samples. The analysis unearthed snoRNAs that appeared to coincide with overall or recurrence-free survival, while highlighting potential interactions between snoRNAs and genes involved in tumor formation.

"These potentially novel biomarkers need to be validated in independent studies to ascertain their role in [breast cancer] prognostication," senior author Sambasivarao Damaraju, a laboratory medicine and pathology researcher affiliated with the University of Alberta and the Cross Cancer Institute, and co-authors wrote, noting that "it is not certain if the 13 prognostic snoRNAs are specific to [breast cancer] or if they share prognostic relevance in other cancer types."

Efforts to identify prognostic markers in cancer have largely focused on factors such as mutation patterns, gene expression signatures, and microRNA profiles, though some groups have started looking at other types of molecular information that might be associated with survival outcomes such as transcript isoform ratios or snoRNA signatures.

Though snoRNAs are best known for housekeeping roles in the cell and for modifying other types of RNA after transcription, the team explained, there are clues that they might provide information for diagnosing some conditions and predicting disease trajectory.

Damaraju and his colleagues noted that "snoRNAs may get processed to other smaller regulatory RNAs such as miRNAs and piwi-interacting RNAs, which are well known as post-transcriptional gene regulators."

To search for potential prognostic markers in breast cancer, the researchers used the Illumina GAIIx to sequence small RNAs in 104 formalin-fixed, paraffin-embedded invasive ductal carcinoma samples and 11 flash-frozen breast tissue samples from healthy individuals undergoing breast reduction surgery.

After excluding five samples with poor quality data or expression patterns that did not cluster with the other cancers, the team compared snoRNA repertoires in cases and controls and did analyses focused on snoRNA associations with overall survival and progression-free survival in the cancer samples alone. The searches led to 13 survival-associated snoRNAs — an overlapping set that included a dozen snoRNAs associated with overall survival and 10 snoRNAs with ties to recurrence-free survival.

The researchers validated two representative snoRNAs — SNORD46 and SNORD89 —by real-time quantitative RT-PCR, demonstrating that expression of these snoRNAs was dialed down in the breast cancer samples compared with normal breast tissue.

When the team took a broader look at the snoRNAs present in the breast cancer samples, meanwhile, it found several examples of snoRNA sequences that overlapped with documented miRNAs or piwi-interacting RNAs, including other small RNAs predicted to have downstream effects on genes implicated in tumor formation.

The authors noted that their differential expression findings "should be interpreted with caution as we used normal samples preserved as [fresh frozen] tissues and tumor samples preserved as FFPE tissues." Even so, they said, fleshing out the potential gene regulatory roles for snoRNAs "could open up new avenues for the development of snoRNAs for diagnostic and therapeutic purposes."