Urine Biomarker Panel Could Detect Early Pancreatic Adenocarcinoma

The combination of LYVE1, REG1A and TFF1 proteins can distinguish between urine samples from patients with stage I to II pancreatic cancer and those from healthy individuals

medwireNews: A panel of three proteins found in urine could prove useful for the detection of stage I to II pancreatic ductal adenocarcinoma (PDAC), research suggests.

“Being completely non-invasive and inexpensive, this urine screening test could, upon further validation, and when coupled with timely surgical intervention, lead to a much improved outcome in patients with high risk of developing pancreatic adenocarcinoma”, write the researchers in Clinical Cancer Research.

They explained in a press release that survival rates fall from 60% for patients diagnosed at stage I to 20% for those with stage II disease at diagnosis.

Proteomic analysis of urine samples from six patients with PDAC and six with chronic pancreatitis as well as six healthy controls identified approximately 1500 non-redundant proteins, of which three – LYVE1, REG1A and TFF1 – were selected for further assessment.

REG1A, a regenerating glycoprotein family member, and TFFI, a gastrointestinal secretory peptide, have previously been linked to PDAC, the researchers explain. LYVE1 is associated with lymphatic endothelium during Lymphangiogenesis in some tumours.

In the training cohort of 143 patients with stage I to IV PDAC and 59 healthy controls, the three biomarkers together discriminated diseased from healthy samples with an area under the receiver operating characteristic curve (AUC) of 0.891. And the AUC in the validation dataset comprising 49 PDAC patients and 28 healthy individuals was 0.921.

Similarly, the panel discriminated stage I to II PDAC from healthy specimens with “high accuracy”, reports the team, with AUCs of 0.900 and 0.926 in the training (56 PDAC patients; 61 controls) and validation (15 PDAC patients; 26 controls) datasets, respectively.

The AUC for comparison of stage I to II PDAC (n=71) versus healthy (n=28) specimens was significantly higher for the panel than for the PDAC Biomarker CA19.9, at 0.973 versus 0.880. Combining the urine biomarker panel with CA19.9 led to a significant increase in AUC to 0.991, but did not improve the comparison of stage I to IIA PDAC (n=16) samples with healthy ones.

Highlighting the need for further validation, Tatjana Crnogorac-Jurcevic, from Queen Mary University of London in the UK, and colleagues suggest testing the panel in high-risk individuals, such as those with at least two affected first-degree relatives or known predisposing genetic abnormalities.

Reference

Radon TP, Massat NJ, Jones R,et al.Identification of a Three-Biomarker Panel in Urine for Early Detection of Pancreatic Adenocarcinoma.Clin Cancer Res2015; 21: 3512–3521. doi: 10.1158/1078-0432.CCR-14-2467 

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