Biomarkers in the diagnosis of pancreatic cancer: Are we closer to finding the golden ticket?

Abstract

Pancreatic cancer (PC) is a leading cause of cancer related mortality on a global scale. The disease itself is associated with a dismal prognosis, partly due to its silent nature resulting in patients presenting with advanced disease at the time of diagnosis. To combat this, there has been an explosion in the last decade of potential candidate biomarkers in the research setting in the hope that a diagnostic biomarker may provide a glimmer of hope in what is otherwise quite a substantial clinical dilemma. Currently, serum carbohydrate antigen 19-9 is utilized in the diagnostic work-up of patients diagnosed with PC however this biomarker lacks the sensitivity and specificity associated with a gold-standard marker. In the search for a biomarker that is both sensitive and specific for the diagnosis of PC, there has been a paradigm shift towards a focus on liquid biopsy and the use of diagnostic panels which has subsequently proved to have efficacy in the diagnosis of PC. Currently, promising developments in the field of early detection on PC using diagnostic biomarkers include the detection of microRNA (miRNA) in serum and circulating tumour cells. Both these modalities, although in their infancy and yet to be widely accepted into routine clinical practice, possess merit in the early detection of PC. We reviewed over 300 biomarkers with the aim to provide an in-depth summary of the current state-of-play regarding diagnostic biomarkers in PC (serum, urinary, salivary, faecal, pancreatic juice and biliary fluid).

Oncogenomic Changes in Pancreatic Cancer and Their Detection in Stool

“…If such lesions, which include pancreatic intraepithelial neoplasms, mucinous cystic neoplasms, IPMNs, and others, are surgically removed before they acquire the ability to invade, development of cancer can be impeded [ 29 , 129 ]. Several factors that differentiate PC from other pancreatic conditions and from healthy individuals, such as serum glycolipids and proteins, inflammatory and growth factors, autoantibodies, cytokines and chemokines, adhesion molecules, metabolites and DNA/RNA-based alterations, have been proposed as novel biomarkers for the early diagnosis of PC [ 11 , 13 , 130 ]. However, these have not yet been implemented in clinical practice, since evidence of their clinical value from large-scale studies is still missing [ 131 ].…”

“…In the past few years, research on PC diagnostics has been focusing on the discovery and evaluation of novel molecular biomarkers. These include serum markers such as enzymes, cytokines, antibodies and antigens, and moreover, nucleic acid-based markers typical for PC [ 11 , 12 , 13 ]. Oncogenomic alterations, such as gene mutations, epigenetic, and transcriptomic changes present in tumor tissue, can also be detected from body fluids in circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), or cell-free DNA and RNA (cfDNA and cfRNA) [ 14 ].…”

Circulating Biomarkers for Therapeutic Monitoring of Anti-cancer Agents

“…68-70 However, notable confounding factors have been described, including its relatedness to Lewis blood group antigens and elevation in the setting of obstructive jaundice. 66 , 71 …”

Diagnostic biomarkers for pancreatic cancer: An update

“…We read with great interest a review paper recently published by O'Neill and Stoita[ 1 ], reviewing diagnostic biomarkers currently applied in pancreatic cancer (PC). The biomarkers are from serum, urinary, pancreatic, salivary, biliary, and fecal sources and comprise many different types of molecules.…”

“…The biomarkers are from serum, urinary, pancreatic, salivary, biliary, and fecal sources and comprise many different types of molecules. For example, serum biomarkers include proteins of glycolipids, growth factors, cytokines, chemokines, adhesion molecules, non-coding RNAs (long non-coding RNAs and microRNAs), and liquid biopsy (exosomes, circulating tumor DNA or ctDNA, and circulating tumor cells or CTCs)[ 1 ].…”