Advances on diagnostic biomarkers of pancreatic ductal adenocarcinoma: A systems biology perspective

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy that is usually diagnosed at an advanced stage when curative surgery is no longer an option. Robust diagnostic biomarkers with high sensitivity and specificity for early detection are urgently needed. Systems biology provides a powerful tool for understanding diseases and solving challenging biological problems, allowing biomarkers to be identified and quantified with increasing accuracy, sensitivity, and comprehensiveness. Here, we present a comprehensive overview of efforts to identify biomarkers of PDAC using genomics, transcriptomics, proteomics, metabonomics, and bioinformatics. Systems biology perspective provides a crucial “network” to integrate multi-omics approaches to biomarker identification, shedding additional light on early PDAC detection.

Prognostic value and potential molecular mechanism of the like-Sm gene family in early-stage pancreatic ductal adenocarcinoma

“…However, because of the deep position of the pancreas, factors such as obesity and intestinal gas, and even the operator's experience, can affect the accuracy of the diagnosis. Therefore, new biomarkers are urgently needed for detection of pancreatic cancer in the early stages (27) protein a-chain (C4BPA), neutrophil gelatinase-associated lipocalin (NGAL) in urine, and others (28). However, CA19-9 is insufficient as an independent diagnostic tool; for instance, serum CA19-9 elevation can occur in patients with benign diseases such as chronic or acute pancreatitis, cholangitis, obstructive jaundice, liver cirrhosis, or other malignancies such as gastrointestinal cancers (29).…”

Diagnostic, Predictive and Prognostic Molecular Biomarkers in Pancreatic Cancer: An Overview for Clinicians

“…Composite markers or scores, focusing on multi-omics approaches [ 147 ] with the concomitant application of computational biology and artificial intelligence principles, can enhance detection accuracy and provide a better robustness. These panels of markers can be initially tested in high-risk patients (smokers, chronic pancreatitis, mucinous neoplasms of the pancreas, and genetic predisposition) before being validated in lower risk patients [ 148 , 149 , 150 ]. This strategy might provide better efficiency and economic effects for the early detection of pancreatic cancer.…”

Current State of “Omics” Biomarkers in Pancreatic Cancer

“…Over the years, microarray and RNAseq technology have been utilized not only to obtain coding but also non-coding RNA signatures. Although transcriptomic studies of non-coding RNAs are mainly focused on microRNAs (miRNA) and long non-coding RNAs (lncRNAs), other non-coding RNA types such as piwi interacting RNA (piRNAs), circular (circRNAs), small nucleolar RNA (snoRNA), and small nuclear RNA (snRNA) [ 35 ] are also promising biomarker candidates as they are quantitatively assessed, providing opportunities for noninvasive and early diagnosis of PDAC [ 20 ].…”

“…The analysis and verification of unique protein biomarkers have been achieved by using highly sensitive and reliable mass spectrometry-based proteomics. Moreover, this technique is crucial in terms of querying protein modifications [ 20 ]. Numerous clinical specimens of pancreatic cancer such as pancreatic juice, pancreatic tumor tissue, pancreatic cyst fluid, urine, and plasma/serum have become targets for the proteomics field to dig into mechanisms of disease, improve novel biomarkers, and enhance drug development [ 76 , 77 , 78 ].…”

“…As a source of pancreatic cancer biomarker, saliva has also been used. In omics biomarker studies, blood is a frequently preferred sample source due to its easy accessibility, noninvasiveness, and cost-effectiveness [ 20 ]. As an alternative rich source for the discovery of biomarkers, pancreatic juice has recently been identified.…”