Pancreatic cancer (PCA) is a neoplasm arising from malignant transformed pancreatic cells which are in 95 % of the cases located in the exocrine glands and therefore belong to adenocarcinomas. Less common are pancreatic cancers that arise from islet cells. It is fifth-most-deadly cancer worldwide and has doubled in incidence during the last 40 years, from 5 to 10 cases per 100,000 persons per year. Diagnosis often comes too late since patients have unspecific symptoms and no reliable PCA-specific marker exists for early diagnosis where life-saving therapy is still possible. Due to this diagnostic limitation, 5-year survival rate is less than 5 % with an average life-expectancy of 6 to 10 months. Due to similar clinical symptoms, PCA is difficult to differentiate from chronic pancreatitis (ChP).

ChP is a progressive inflammation of the pancreas leading to irreversible destruction of the pancreatic tissue. ChP is in most of the cases caused by excessive alcohol consumption. Its incidence varies from 2 to 23 cases per 100,000 persons and year depending on geographic region and socio-economic geographic characteristics. It is frequently indistinguishable from PCA, but in case of diagnostic certainty will be treated conservatively rather than by surgery as in the case of PCA.

The purpose of a case-control study conducted by Mosaiques together with the gastroenterology department of the Hannover Medical School in 2015 was to search for peptide markers in urine that are differentially regulated between PCA and ChP and to include the most discriminative ones to a multimarker model for accurate differentiation of malignant and benign disorders of the pancreas. In an independent validation cohort consisting of 49 patients with PCA and 52 patients with ChP, a urinary peptide marker model composed of 47 peptide fragments had an AUC of 0.93. At the optimum cut-off, sensitivity and specificity of the test were 87% and 85%, respectively. Application of the proteomic test improved the sensitivity of classification by 23% (at -0.02 as cut-off) compared to the tumor marker CA19-9.

Distribution of classification scores by the urinary peptide marker panel was investigated in stratified ChP patients with CA19-9 serum levels > 99 U/ml (n=5, high group) and in stratified PCA patients with CA19-9 serum levels < 99 U/ml (n=19, low group). Applying the cut-off of -0.02, classification by the proteomic test resulted in a sensitivity of 74% (14 out of 19 true positive PCA determinations) and a specificity of 80% (4 out of 5 true negative ChP determinations) on this stratified subsample of CA19-9 false classifications.

In conclusion, proteomic analysis of urine differentiates PCA from ChP. Urine proteome analysis may be useful for proving PCA in unclear cases and for surveillance of patients with ChP. As indicated by in silico protease prediction and subsequent enzyme immunoassay and immunohistochemistry validation the peptide fragments identified by proteome analysis serve as surrogate markers for the underlying disease process. 

References

Schönemeier B, Metzger J, Klein J, et al. Urinary peptide analysis differentiates pancreatic cancer from chronic pancreatitis. Pancreas. 2016; 45: 1018-26.