Non-Invasive Biomarkers for Earlier Detection of Pancreatic Cancer-A Comprehensive Review.

Published on May 31, 2021in Cancers6.126
· DOI :10.3390/CANCERS13112722
Greta Brezgyte (QMUL: Queen Mary University of London), Vinay Shah (QMUL: Queen Mary University of London)+ 1 AuthorsTatjana Crnogorac-Jurcevic34
Estimated H-index: 34
(QMUL: Queen Mary University of London)
Source
Abstract
Pancreatic ductal adenocarcinoma (PDAC) carries a deadly diagnosis, due in large part to delayed presentation when the disease is already at an advanced stage. CA19-9 is currently the most commonly utilized biomarker for PDAC; however, it lacks the necessary accuracy to detect precursor lesions or stage I PDAC. Novel biomarkers that could detect this malignancy with improved sensitivity (SN) and specificity (SP) would likely result in more curative resections and more effective therapeutic interventions, changing thus the present dismal survival figures. The aim of this study was to systematically and comprehensively review the scientific literature on non-invasive biomarkers in biofluids such as blood, urine and saliva that were attempting earlier PDAC detection. The search performed covered a period of 10 years (January 2010-August 2020). Data were extracted using keywords search in the three databases: MEDLINE, Web of Science and Embase. The Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool was applied for study selection based on establishing the risk of bias and applicability concerns in Patient Selection, Index test (biomarker assay) and Reference Standard (standard-of-care diagnostic test). Out of initially over 4000 published reports, 49 relevant studies were selected and reviewed in more detail. In addition, we discuss the present challenges and complexities in the path of translating the discovered biomarkers into the clinical setting. Our systematic review highlighted several promising biomarkers that could, either alone or in combination with CA19-9, potentially improve earlier detection of PDAC. Overall, reviewed biomarker studies should aim to improve methodological and reporting quality, and novel candidate biomarkers should be investigated further in order to demonstrate their clinical usefulness. However, challenges and complexities in the path of translating the discovered biomarkers from the research laboratory to the clinical setting remain and would have to be addressed before a more realistic breakthrough in earlier detection of PDAC is achieved.
References113
Newest
#1Neil B. Marya (Mayo Clinic)H-Index: 7
#2Patrick D. PowersH-Index: 2
Last. Michael J. Levy (Mayo Clinic)H-Index: 107
view all 20 authors...
Objective The diagnosis of autoimmune pancreatitis (AIP) is challenging. Sonographic and cross-sectional imaging findings of AIP closely mimic pancreatic ductal adenocarcinoma (PDAC) and techniques for tissue sampling of AIP are suboptimal. These limitations often result in delayed or failed diagnosis, which negatively impact patient management and outcomes. This study aimed to create an endoscopic ultrasound (EUS)-based convolutional neural network (CNN) model trained to differentiate AIP from ...
13 CitationsSource
#1Silvana Debernardi (QMUL: Queen Mary University of London)H-Index: 17
#2Harrison O’Brien (QMUL: Queen Mary University of London)H-Index: 1
Last. Tatjana Crnogorac-Jurcevic (QMUL: Queen Mary University of London)H-Index: 34
view all 16 authors...
Publisher Copyright: © 2020 Debernardi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
4 CitationsSource
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 ...
6 CitationsSource
#1David CrosbyH-Index: 1
#2Nicole LyonsH-Index: 1
Last. Early DetectionH-Index: 1
view all 10 authors...
16 CitationsSource
#1Andrew T. MagisH-Index: 23
#2Noa RappaportH-Index: 12
Last. Nathan D. PriceH-Index: 65
view all 7 authors...
We analyzed 1196 proteins in longitudinal plasma samples from participants in a commercial wellness program, including samples collected pre-diagnosis from ten cancer patients and 69 controls. For three individuals ultimately diagnosed with metastatic breast, lung, or pancreatic cancer, CEACAM5 was a persistent longitudinal outlier as early as 26.5 months pre-diagnosis. CALCA, a biomarker for medullary thyroid cancer, was hypersecreted in metastatic pancreatic cancer at least 16.5 months pre-dia...
1 CitationsSource
#1Indu Khatri (Harvard University)H-Index: 10
#2Manoj BhasinH-Index: 49
Pancreatic ductal adenocarcinoma (PDAC) is generally incurable due to the late diagnosis and absence of markers that are concordant with expression in several sample sources (i.e., tissue, blood, plasma) and platforms (i.e., Microarray, sequencing). We optimized meta-analysis of 19 PDAC (tissue and blood) transcriptome studies from multiple platforms. The key biomarkers for PDAC diagnosis with secretory potential were identified and validated in different cohorts. Machine learning approach i.e.,...
3 CitationsSource
#1Zijian Yang (Applied Science Private University)H-Index: 8
#2Michael J. LaRiviere (UPenn: University of Pennsylvania)H-Index: 7
Last. Erica L. Carpenter (UPenn: University of Pennsylvania)H-Index: 22
view all 19 authors...
Purpose: To determine whether a multi-analyte liquid biopsy can improve the detection and staging of pancreatic adenocarcinoma (PDAC). Experimental Design: We analyzed plasma from 204 subjects (71 healthy, 44 non-PDAC pancreatic disease, and 89 PDAC) for the following biomarkers: Tumor-associated extra-cellular vesicle (EV) miRNA and mRNA isolated on a nanomagnetic platform that we developed and measured by next-generation sequencing or qPCR, circulating cell-free DNA (ccfDNA) concentration meas...
13 CitationsSource
#1Stephen P. Pereira (UCL: University College London)H-Index: 61
#2Lucy Oldfield (University of Liverpool)H-Index: 4
Last. Eithne Costello (University of Liverpool)H-Index: 51
view all 14 authors...
Pancreatic ductal adenocarcinoma is most frequently detected at an advanced stage. Such late detection restricts treatment options and contributes to a dismal 5-year survival rate of 3-15%. Pancreatic ductal adenocarcinoma is relatively uncommon and screening of the asymptomatic adult population is not feasible or recommended with current modalities. However, screening of individuals in high-risk groups is recommended. Here, we review groups at high risk for pancreatic ductal adenocarcinoma, inc...
56 CitationsSource
#1Minetta C. Liu (Mayo Clinic)H-Index: 23
#2Geoffrey R. Oxnard (Harvard University)H-Index: 60
Last. Michael V. SeidenH-Index: 45
view all 157 authors...
Background Early cancer detection could identify tumors when outcomes are superior at a time when outcomes are superior and treatment is less morbid. This prospective case-control sub-study (from NCT02889978 and NCT03085888) assessed the performance of targeted methylation analysis of circulating cell-free DNA (cfDNA) to detect and localize multiple cancer types across all stages at high specificity. Participants and methods The 6689 participants [2482 cancer (>50 cancer types), 4207 non-cancer]...
214 CitationsSource
#1Wilson Luiz da Costa (BCM: Baylor College of Medicine)H-Index: 10
#2Abiodun Oluyomi (BCM: Baylor College of Medicine)H-Index: 5
Last. Aaron P. Thrift (BCM: Baylor College of Medicine)H-Index: 7
view all 3 authors...
Background Pancreatic ductal adenocarcinoma is a major contributor to cancer-related mortality in the United States. We aimed to investigate trends in incidence rates from all 50 states from 2001 to 2016, overall and by race, sex, and state and using age-period-cohort analyses. Methods Age-adjusted incidence rates and trends in adults aged 35 years and older were calculated using data from the US Cancer Statistics registry. We used joinpoint regression to compute annual percent changes (APC) and...
2 CitationsSource
Cited By3
Newest
Source
#1Rosel Kretschmer-Kazemi Far (University of Lübeck)H-Index: 8
#2Kirsten Frank (University of Lübeck)H-Index: 6
Last. Georg Sczakiel (University of Lübeck)H-Index: 27
view all 3 authors...
Body fluids in the context of cancer diagnosis are the primary source of liquid biopsy, i.e., biomarker detection that includes blood and serum, urine, and saliva. RNA represents a particular class of biomarkers because it is thought to monitor the current status of gene expression in humans, in organs, and if present, also in tumors. In case of bladder cancer, we developed a scheme that describes, in detail, all steps from the collection of urine samples from patients, stabilization of samples,...
Source
#1Johannes Byrling (Lund University)H-Index: 3
#2Katarzyna Said Hilmersson (Lund University)H-Index: 9
Last. Bodil Andersson (Lund University)H-Index: 24
view all 5 authors...
Distal cholangiocarcinoma and pancreatic ductal adenocarcinoma are malignancies with poor prognoses that can be difficult to distinguish preoperatively. Thrombospondin-2 has been proposed as a novel diagnostic biomarker for early pancreatic ductal adenocarcinoma. The aim of the present study was to evaluate thrombospondin-2 as a diagnostic and prognostic biomarker in combination with current biomarker CA 19-9 for distal cholangiocarcinoma and pancreatic ductal adenocarcinoma. Thrombospondin-2 wa...
Source