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Baylor, Collaborators Pinpoint Potential Prognostic snoRNA Biomarker for Colorectal Cancer

NEW YORK (GenomeWeb) — A team led by researchers from the Baylor University Medical Center has identified a small nucleolar RNAs that shows promise as a biomarker for recurrence and shorter survival in colorectal cancer patients.

After lung cancer, colorectal cancer is the most commonly diagnosed cancer in the world and the most common cause of cancer death in Europe and the US. But despite treatment advances, cancer often returns which is the primary cause of death.

Small nucleolar RNAs, or snoRNAs, are non-coding RNA derivatives and are involved in cell regulation and the development of certain types of cancer. Recent studies have suggested that snoRNAs and other non-coding RNAs may have prognostic impact and biomarker potential in solid cancers. "The investigation of snoRNAs as potential biomarkers and drivers of disease progression represents an unexplored area of cancer biology and has enormous potential clinical significance," the researchers wrote in a statement.

As described yesterday in the journal Gut, the research team, which also included scientists from the Baylor Research Institute and two Japanese institutions, assessed the expression of four different snoRNAs in 274 tissue samples in a bid to find out if snoRNAs signal the likelihood of disease recurrence and associated survival. The tissue samples included 250 taken from the tumors of cancer patients and 24 taken from normal healthy cells lining the gut.

The team extracted total RNA from formalin-fixed paraffin-embedded specimens using Thermo Fisher Scientific Ambion total nucleic acid isolation kits, and performed microdissection on the tissue slides to enrich for tumor cells. Expression of snoRNAs was analyzed using Thermo Fisher Applied Biosystems Custom TaqMan small RNA assays and the average expression levels of snoRNAs were normalized against miR-16, which was previously shown to be a suitable reference gene for relative quantification of small non-coding RNAs. The group also performed in situ hybridization with the Exiqon SNORA42 probe as described in previous research.

The researchers focused on four snoRNAs (SNORD76, SNORD78, ACA11, and SNORA42) that have been reported to be upregulated in cancerous tissues, and showed that they were present in significantly higher and clearly differentiated levels in cancerous cells than they were in normal cells.  

SNORD76, SNORD78, and ACA11 did not significantly correlate with survival or any other clinicopathological factors.  But higher levels of SNORA42 were associated with overall and disease-free survival, and emerged as a risk factor for the return of cancer in another part of the body. It was also correlated with high risk of recurrence and shorter survival in a smaller sample of bowel cancer patients in early stages of their disease.

Additional tests showed that high levels of SNORA42 in cancer cells grown in the laboratory were related to uncontrolled cell division, spread to other areas, invasion of healthy tissue, increased resistance to programmed cell deaths and tumor growth. "Taken together, these results underscore the potential of SNORA42 expression as a useful biomarker for selecting high-risk patients that may receive more personalized treatments in future," the researchers wrote.