Dataset Information

Diagnostic Accuracy of Blood-based Biomarkers for Pancreatic Cancer: A Systematic Review and Meta-analysis.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate below 5%. Carbohydrate antigen 19-9 (CA19-9) is the most commonly used blood-based biomarker for PDAC in current clinical practice, despite having been shown repeatedly to be inaccurate and have poor diagnostic performance. This review aims to assess the reported diagnostic accuracy of all blood-based biomarkers investigated to date in PDAC, by directly comparing individual biomarkers and multi-biomarker panels, both containing CA19-9 and not (novel). A systematic review was conducted in accordance with PRISMA standards in July 2020. Individualized search strategies for three academic databases identified 5,885 studies between the years 1973 and 2020. After two rounds of screening, 250 studies were included. Data were extracted and assessed for bias. A multivariate three-level meta-analysis with subgroup moderators was run in R using AUC values as effect size. On the basis of this model, the pooled AUC value for all multi-biomarker panels (AUC = 0.898; 95% confidence interval (CI): 0.88-0.91) was significantly higher than all single biomarkers (AUC = 0.803; 95% CI: 0.78-0.83; P < 0.0001). The pooled AUC value for CA19-9 alone was significantly lower compared with the multi-biomarker panels containing CA19-9 (P < 0.0001). For the novel biomarkers, the pooled AUC for single biomarkers was also significantly lower compared with multi-biomarker panels (P < 0.0001). Novel biomarkers that have been repeatedly examined across the literature, such as TIMP-1, CEA, and CA125, are highlighted as promising. These results suggest that CA19-9 may be best used as an addition to a panel of biomarkers rather than alone, and that multi-biomarker panels generate the most robust results in blood-based PDAC diagnosis.

Significance

In a systematic review and three-level multivariate meta-analysis, it is shown for the first time that blood-based multi-biomarker panels for the diagnosis of PDAC exhibit superior performance in comparison with single biomarkers. CA19-9 is demonstrated to have limited utility alone, and to perform poorly in patient control cohorts of both healthy and benign individuals. Multi-biomarker panels containing CA19-9 produce the best diagnostic performance overall.

SUBMITTER: Kane LE

PROVIDER: S-EPMC10035398 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Diagnostic Accuracy of Blood-based Biomarkers for Pancreatic Cancer: A Systematic Review and Meta-analysis.

Kane Laura E LE Mellotte Gregory S GS Mylod Eimear E O'Brien Rebecca M RM O'Connell Fiona F Buckley Croí E CE Arlow Jennifer J Nguyen Khanh K Mockler David D Meade Aidan D AD Ryan Barbara M BM Maher Stephen G SG

Cancer research communications 20221020 10

Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate below 5%. Carbohydrate antigen 19-9 (CA19-9) is the most commonly used blood-based biomarker for PDAC in current clinical practice, despite having been shown repeatedly to be inaccurate and have poor diagnostic performance. This review aims to assess the reported diagnostic accuracy of all blood-based biomarkers investigated to date in PDAC, by directly comparing individual biomarkers and multi-biomarker panels, both containing C ...[more]

PMID: 36969742

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Project description:BackgroundEarly, non-invasive identification can generally enhance the survival rate for asymptomatic pancreatic cancer (PC). This systematic review and meta-analysis is conducted to evaluate the precision of diagnosing PC using serum and duodenal fluid exosomes.MethodsFollowing the guidelines of PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analyses), searches were conducted in the PubMed, Embase, Cochrane Library, and Web of Science databases in April 2024. A study was considered appropriate if it provided diagnostic precision and accuracy for patients with pancreatic cancer. The combined diagnostic impact was assessed by calculating the area beneath the aggregated SROC curve, and the quality of the studies included was evaluated using the QUADAS-2 checklist. All statistical evaluations and graphical representations utilized STATA 14.0.ResultsEmploying the terms "exosomes" and "pancreatic cancer" along with the search methodology, research was conducted across PubMed, Web of Science, Cochrane, and Embase databases. A total of 1202 studies were extracted from the databases, out of which nine were ultimately selected based on specific inclusion and exclusion standards. Across eight studies, exosomes were isolated from serum, while in a different one, they were taken from duodenal fluid. This document conducts subgroup analyses focusing on various types of exosome biomarkers, their origins, isolation techniques, and methods for analyzing biomarkers. Within the subset of exosome biomarker types, the group with exosomal cell surface proteoglycan exhibited the greatest combined sensitivity (0.96 (95% CI = 0.81-0.99) and specificity (0.90 (95% CI = 0.83-0.95)). Additionally, the set of exosomal cell surface proteoglycans showed the highest aggregated diagnostic ratio (215.92), combined positive likelihood ratio (9.96), area under the curve (0.93), and kombiniertes negative Likelihood-Ratio (0.05). The combined sensitivity of serum-derived exosomes stood at (0.86 (95% CI = 0.77-0.92)), the collective specificity at (0.83 (95% CI = 0.77-0.89)), the aggregate positive likelihood ratio at (5.22), the combined diagnostic ratio at (31.48), the overall area beneath the curve at (0.91), and the combined negative likelihood ratio at (0.17). Within the subgroup examination of exosome isolation techniques, ultracentrifugation emerged as the most sensitive method (0.90 (95% CI = 0.74-0.97)), the most specific method (0.89 (95% CI = 0.83-0.93)), the top positive likelihood ratio (8.35), the highest diagnostic ratio (76.48), the largest combined curve area (0.92), and the smallest negative likelihood ratio (0.11) in the aggregated data. Within the subset of biomarker analysis methods, the aggregate sensitivity via qRT-PCR was (0.84 (95% CI = 0.74-0.90)), the collective specificity (0.78 (95% CI = 0.64-0.87)), the aggregate diagnostic ratio (18.11), the aggregate area under the curve (0.88), the aggregate positive likelihood ratio (3.77), and the combined negative likelihood ratio (0.21).ConclusionOverall, exosomes are still valuable in the diagnosis of pancreatic cancer. In subgroup analyses, the proteoglycan found on exosomal cell surfaces is highly valuable for diagnosing pancreatic cancer. The more frequent separation method used in the nine included studies was ultracentrifugation, and it did demonstrate good data. Nonetheless, to verify their practicality and usefulness in clinical environments, a significant amount of clinical trials are still necessary.

Project description:BackgroundNovel blood-based protein biomarkers may be of value for efficient, accurate, and non-invasive diagnosis of pancreatic cancer. This study assesses the diagnostic accuracy of newly recognized blood-based protein biomarkers for detecting pancreatic cancer, and investigates their added value to CA19-9, the common blood-based biomarker in clinical use for pancreatic cancer.MethodsPubMed, Embase, Web of Science, and the Wiley/Cochrane Library were systematically searched from inception until June 2022. A meta-analysis of aggregate and individual participant data was conducted using frequentist and Bayesian hierarchical random-effects models. The added clinical utility of protein biomarkers was investigated using bootstrap bias-corrected decision curve analyses.FindingsAggregate data from 28 primary studies (6127 participants) were included, of which 8 studies (1790 participants) provided individual participant data. CA19-9 was significantly more accurate than MIC-1 for distinguishing pancreatic cancer from benign disease (AUC, 0.83 vs 0.74; relative diagnostic odds ratio [rDOR], 2.10 [95% CI, 0.98-4.48]; p = 0.002), THBS2 (AUC, 0.87 vs 0.69; rDOR, 4.53 [2.16-9.39]; p < 0.0001), TIMP-1 (AUC, 0.91 vs 0.70; rDOR, 8.00 [3.81-16.9]; p < 0.0001), OPN (AUC, 0.89 vs 0.74; rDOR, 4.22 [1.13-15.6]; p < 0.0001), ICAM-1 (AUC, 0.91 vs 0.68; rDOR 9.30 [0.87-99.5]; p < 0.0001), and IGFBP2 (AUC, 0.91 vs 0.68; rDOR, 4.48 [0.78-24.3]; p < 0.0001). The addition of these novel protein biomarkers to CA19-9 did not significantly improve the AUC, and resulted in minor increases or limited decreases in clinical utility.InterpretationNovel protein biomarkers have moderate diagnostic accuracy, do not outperform CA19-9 in differentiating pancreatic cancer from benign disease, and show limited added clinical value to CA19-9. We propose recommendations to aid the development of minimally invasive diagnostic tests with sufficient clinical utility to improve the management of patients with suspected pancreatic cancer.FundingBennink Foundation, Dutch Cancer Foundation (KWF Kankerbestrijding), and AIRC.

Project description:IntroductionColorectal cancer (CRC) is the third most diagnosed cancer and the second most common cause of cancer mortality worldwide. Most CRCs develop through either the adenoma-to-carcinoma or the serrated pathways, and, therefore, detection and removal of these precursor lesions can prevent the development of cancer. Current screening programmes can aid in the detection of CRC and adenomas; however, participation rates are suboptimal. Blood-based biomarkers may help to address these low participation rates in screening programmes. Although blood-based biomarker tests show promise for cancer detection, limited attention has been placed on the sensitivity and specificity for detection of the precursor lesions. The aim of this research is to conduct a systematic review and meta-analysis to evaluate the accuracy of blood-based biomarker tests in detecting advanced precancerous lesions.Methods and analysisThis protocol was informed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) and results will be reported in line with the PRISMA guidelines. Literature searches will be conducted on PubMed, Embase and Web of Science. Two reviewers will conduct the searches, and independently screen them, according to title and abstract and then the full-text versions of those selected articles as well as the risk of bias via the Quality Assessment of Diagnostic Accuracy Studies version 2 (QUADAS-2) tool. The Grading of Recommendations Assessment, Development and Evaluation guidelines will be used to validate the certainty of evidence for recommendations based on the risk of bias findings. Meta-analysis will be conducted where appropriate on groups of studies with low heterogeneity.Ethics and disseminationNo patient data will be included in our review and, therefore, ethics approval is not required. It is anticipated that the review will identify the most promising candidate biomarkers for clinical translation in the screening of advanced precancerous lesions. The results will be published in a peer-reviewed journal.Prospero registration numberCRD42021285173.

Dataset Information

Diagnostic Accuracy of Blood-based Biomarkers for Pancreatic Cancer: A Systematic Review and Meta-analysis.

Significance

Publications

Diagnostic Accuracy of Blood-based Biomarkers for Pancreatic Cancer: A Systematic Review and Meta-analysis.

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