MicroRNA Panel Distinguishes Between High- and Low-Risk Pancreatic Lesions

A panel of six microRNAs (miRNAs) has been identified that can distinguish between high-risk and low-risk pancreatic lesions that are capable of progressing to full-blown cancer of the pancreas.

Intraductal papillary mucinous neoplasms (IPMNs) are precursors of the form of cancer of the pancreas called pancreatic ductal adenocarcinoma (PDAC). Differentiating between high-risk IPMNs that warrant surgical resection and low-risk IPMNs that can be monitored has been a significant clinical problem.

Pancreatic cancer is the fourth most common cause of cancer death in the Western world. The prognosis is poor, with one- and five-year survival rates of only 20% and 6%, respectively. To aid in early detection of pancreatic cancer, investigators at the Moffitt Cancer Center (Tampa, FL, USA) used advanced genomic tools to analyze the miRNAs associated with low-risk and high-risk IPMNs.

MiRNAs comprise a family of small noncoding 19- to 25-nucleotide RNAs that regulate gene expression by targeting mRNAs in a sequence specific manner, inducing translational repression or mRNA degradation, depending on the degree of complementarity between miRNAs and their targets. Many miRNAs are conserved in sequence between distantly related organisms, suggesting that these molecules participate in essential processes. In fact, miRNAs have been shown to be involved in the regulation of gene expression during development, cell proliferation, apoptosis, glucose metabolism, stress resistance, and cancer.

The investigators performed genome-wide miRNA expression profiling on 28 surgically-resected, pathologically-confirmed IPMNs (19 high-risk, nine low-risk) using Life Technologies (Carlsbad, CA, USA) Taqman MicroRNA Arrays. A validation phase was performed in 21 independent IPMNs (13 high-risk, 8 low-risk). They also explored associations between miRNA expression level and various clinical and pathological factors and examined genes and pathways regulated by the identified miRNAs by integrating data from bioinformatic analyses and microarray analysis of miRNA gene targets.

Results revealed that six miRNAs (miR-100, miR-99b, miR-99a, miR-342-3p, miR-126, miR-130a) were downregulated in high-risk versus low-risk IPMNs and distinguished between these groups. The same trend was observed in the validation phase of the study. Low miR-99b expression was associated with main pancreatic duct involvement, and serum albumin levels were positively correlated with miR-99a and miR-100 expression.

“Importantly, this research may also help foster the development of new prevention and early detection strategies for pancreatic cancer,” said senior author Dr. Mokenge P. Malafa, chairman of the department of gastrointestinal oncology at the Moffitt Cancer Center. “We also provided evidence that the six microRNAs may contribute to pancreatic cancer progression.”

Related Links:
Moffitt Cancer Center
Life Technologies