Abstract
BackgroundPatients with pancreatic ductal adenocarcinoma (PDAC) have late diagnosis which results in poor prognosis. Currently, surgical resection is the only option for curative intent. Identifying high-risk features for patients with aggressive PDAC is essential for accurate diagnosis, prognostication, and personalised care due to the disease burden and risk of recurrence despite surgical resection. A panel of three biomarkers identified in tumour tissue (S100A4, Ca125 and Mesothelin) have shown an association with poor prognosis and overall survival. The diagnostic and prognostic value of the serum concentration of this particular biomarker panel for patients with PDAC has not been previously studied.MethodsRetrospectively collected blood samples of PDAC patients (n =120) and healthy controls (n =80) were evaluated for the serum concentration of select biomarkers – S100A4, S100A2, Ca-125, Ca 19-9 and mesothelin. Statistical analyses were performed for diagnostic and prognostic correlation.ResultsA panel of four biomarkers (S100A2, S100A4, Ca-125 and Ca 19-9) achieved high diagnostic potential (AUROC 0.913). Three biomarkers (S100A4, Ca-125 and Ca 19-9) correlated with poor overall survival in a univariable model (p < 0.05). PDAC patients with abnormal levels of 2 or more biomarkers in their serum demonstrated significantly lower survival compared to patients with abnormal levels of one or less biomarker (p < 0.05).Conclusion and ImpactThe identified biomarker panels have shown the potential to diagnose PDAC patients and stratify patients based on their prognostic outcomes. If independently validated, this may lead to the development of a diagnostic and prognosticating blood test for PDAC.
Highlights
Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality of all major cancers and is projected to become the second most common cause of cancer related death by 2030 [1, 2]
A PDAC tissue biomarker panel (S100A4, Mesothelin, Ca125) approach has recently been shown to be successful in prognosticating pancreatic cancer outcome [5]
The aim of this study was to: [1] determine the diagnostic potential of this set of biomarkers individually and as a panel by comparing serum expression of these biomarkers in PDAC patients and healthy controls; [2] establish a “normal” and “abnormal” result for the expression of a set of biomarkers – Ca 19.9, Ca-125, Mesothelin, S100A2 and S100A4 by comparing serum values in patients with PDAC with healthy controls; [3] identifying the prognostic significance of these biomarkers based on serum expression in PDAC patients and correlation with overall survival
Summary
Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality of all major cancers and is projected to become the second most common cause of cancer related death by 2030 [1, 2]. A PDAC tissue biomarker panel (S100A4, Mesothelin, Ca125) approach has recently been shown to be successful in prognosticating pancreatic cancer outcome [5] The expression of these biomarkers in the tumour tissue has been shown to track with the genetic changes associated with a more aggressive (so called ‘squamous’) genotype of PDAC [6]. Given that these tissue sample may be difficult to obtain at first presentation, a liquid biopsy using secreted biomarkers in the patient’s blood would be beneficial in diagnosis and prognostication with personalisation of treatment for patients with PDAC. The diagnostic and prognostic value of the serum concentration of this particular biomarker panel for patients with PDAC has not been previously studied
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