Urinary Biomarkers for the early detection of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers, with a median survival time of 5-6 months and only 5% of individuals surviving more than 5 years. This high mortality rate is primarily caused by the late diagnosis as, in the early stage, when tumours are still small and patients amenable for surgery, the disease is asymptomatic and remains largely undetected. The early diagnosis using an innovative, cost effective and non-invasive detection tool is therefore critical for improving the survival chances of pancreatic cancer patients.

With this in aim, we plan to identify a panel of highly specific and sensitive biomarkers in urine samples. In particular, we are searching for novel class of recently discovered, evolutionary conserved small non-coding RNA molecules called microRNAs (miRNAs), which are highly stable and can be extracted and quantified also in the urine specimens. The potential of microRNAs in PDAC has not been explored yet in urine, although this body fluid represents an attractive alternative to plasma and serum, as it allows frequent and truly non-invasive sampling. In the preliminary work, we have already shown that we can successfully and reliably extract low molecular weight (LMW) RNAs, including miRNAs, from urine samples.

We propose to establish a comprehensive profile of miRNAs in urine, using samples derived from the patients affected with pancreatic cancer and patients with benign inflammatory disease, chronic pancreatitis, and contrast them with miRNA profiles from healthy individuals. On the basis of this data, we will select a panel of most differentially expressed miRNAs between the experimental groups that will subsequently be tested in a large number of additional urine samples.

A best discriminatory biomarkers with the highest specificity and sensitivity will form a basis for the development of a completely non-invasive, diagnostic assay that will then be further validated in a separate, large multicentric validation trial before it can be used for the screening of the high-risk population, such as members of pancreatic cancer families, patients with chronic pancreatitis and adults displaying sudden onset diabetes mellitus.

It is our belief that selected and fully validated miRNA biomarkers in urine will have a true potential for seamless and cost-effective translation into the clinical setting.

Results

The utlity of miRNA biomarkers for non-invasive early detection of PDAC in urine specimens has been demonstrated for the first time. Further study is required.

Charlotte Andersen