A Panel of MicroRNA Biomarkers Augments CA19-9 for Early Diagnosis of Pancreatic Cancer

Cancer researchers have identified panels of microRNAs (miRNAs) that may improve the ability of the currently used protein biomarker CA19-9 to diagnose pancreatic cancer at an early stage.

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. Therefore, markers of the disease that could help with early diagnosis are needed to improve the prognosis.

Investigators at Copenhagen University Hospital (Herlev, Denmark) searched for differences in miRNA expression in whole blood between patients with pancreatic cancer, chronic pancreatitis, and healthy participants in order to identify panels of miRNAs for use in diagnosis of pancreatic cancer compared with the cancer antigen 19-9 (CA19-9), which is elevated in approximately 80% of patients with pancreatic cancer. However, guidelines from the American Society of Clinical Oncology discourage the use of CA19-9 as a screening test for pancreatic cancer. The reason is that the test may be falsely normal (false negative) in many cases, or abnormally elevated in people who have no cancer at all (false positive). The main use of CA19-9 is therefore to see whether a pancreatic tumor is secreting it; if that is the case, then the levels should fall when the tumor is treated, and they may rise again if the disease recurs. In patients with pancreatic masses, CA19-9 can be useful in distinguishing between cancer and other diseases of the gland.

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 conducted a case-control study that included 409 patients with pancreatic cancer and 25 with chronic pancreatitis who had been included prospectively in the Danish BIOPAC (Biomarkers in Patients with Pancreatic Cancer) study (July 2008–October 2012) plus 312 blood donors as healthy participants.

Results revealed that 38 miRNAs in whole blood were significantly dysregulated in patients with pancreatic cancer compared with controls. These miRNAs were further tested, and two diagnostic panels were constructed comprising four miRNAs in index I (miR-145, miR-150, miR-223, and miR-636) and 10 in index II (miR-26b, miR-34a, miR-122, miR-126, miR-145, miR-150, miR-223, miR-505, miR-636, and miR-885.5p).

The results indicated that the two diagnostic panels could distinguish patients with pancreatic cancer from healthy controls. Nonetheless, further research is necessary to understand whether these have clinical implications for early detection of pancreatic cancer and how much this information adds to serum CA19-9.

The study was published in the January 22/29, 2014, issue of the Journal of the American Medical Association.

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