Serum Biomarker Panel for Diagnosis and Prognosis of Pancreatic Ductal Adenocarcinomas

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.

Characterization of Mesothelin Glycosylation in Pancreatic Cancer: Decreased Core Fucosylated Glycoforms in Pancreatic Cancer Patients’ Sera

“…The Cf-MSLN has the potential to discriminate the PaC from the control patients, while, in the same cohort, the protein MSLN levels do not have this ability, as reported by other authors [ 50 , 53 ]. These results emphasize the need for further studies evaluating Cf-MSLN in a larger cohort of patients, and including sera from other types of cancers in order to evaluate its specificity for PaC.…”

“…In addition, the analysis of the circulating mesothelin levels in blood was proposed for PaC diagnosis. However, despite the fact that MSLN was increased in PaC patients vs. healthy individuals (from 0.58 nmol/mL to 0.66 nmol/mL) [ 52 ], it showed no utility in the diagnosis of PaC, due to low sensitivity and specificity values [ 50 , 53 ].…”

Fast and Sensitive Quantification of AccQ-Tag Derivatized Amino Acids and Biogenic Amines by UHPLC-UV Analysis from Complex Biological Samples

“…Regarding the fluids of the human body, serum represents the most commonly used biological material in the medical sciences for the diagnosis of different pathological changes and for the follow-up of applied therapies. Serum is a protein and metabolite rich body fluid that can be obtained in a minimally-invasive manner and is an important source for biomarker analyses [ 28 , 29 ].…”

Prognostic Value of Elevated Pre-treatment Serum CA-125 in Epithelial Ovarian Cancer: A Meta-Analysis

“…CA-125 was found to be an excellent prognostic indicator in a recent investigation on non-gynecologic cancer metastasis to the ovary ( 52 ), and another study revealed that CA-125 was a prognostic factor for survival in patients with gynecologic tumor brain metastases ( 53 ). Several other studies have also shown that pre-treatment serum CA-125 is an independent prognostic factor in patients with bladder urothelial carcinoma (UCB) ( 54 ), pancreatic ductal adenocarcinoma ( 55 ), and renal cell carcinoma ( 56 ). Here, we demonstrate the prognostic efficacy of CA-125 relative to OS and PFS in EOC, which is consistent with findings in other cancer types.…”