Diagnostic accuracy and added value of blood-based protein biomarkers for pancreatic cancer: A meta-analysis of aggregate and individual participant data

被引:26
作者
Boyd, Lenka N. C. [1 ,2 ,3 ]
Ali, Mahsoem [1 ,2 ,3 ]
Leeflang, Mariska M. G. [4 ]
Treglia, Giorgio [5 ,6 ,7 ]
de Vries, Ralph [8 ]
Le Large, Tessa Y. S. [9 ]
Besselink, Marc G. [3 ,10 ]
Giovannetti, Elisa [2 ,3 ,11 ]
van Laarhoven, Hanneke W. M. [3 ,12 ]
Kazemier, Geert [1 ,3 ]
机构
[1] Locat Vrije Univ, Dept Surg, Amsterdam UMC, Amsterdam, Netherlands
[2] Locat Vrije Univ, Dept Med Oncol, Lab Med Oncol, Amsterdam UMC, Amsterdam, Netherlands
[3] Canc Ctr Amsterdam, Imaging & Biomarkers, Amsterdam, Netherlands
[4] Locat Univ Amsterdam, Dept Epidemiol & Data Sci, Amsterdam UMC, Amsterdam, Netherlands
[5] Ente Osped Cantonale, Imaging Inst Southern Switzerland, Clin Nucl Med, Bellinzona, Switzerland
[6] Lausanne Univ Hosp, Dept Nucl Med & Mol Imaging, Lausanne, Switzerland
[7] Univ Svizzera Italiana, Fac Biol & Med, Lugano, Switzerland
[8] Locat Vrije Univ, Med Lib, Amsterdam UMC, Amsterdam, Netherlands
[9] Dijklander Ziekenhuis Locat Hoorn, Dept Surg, Hoorn, Netherlands
[10] Locat Univ Amsterdam, Dept Surg, Amsterdam UMC, Amsterdam, Netherlands
[11] Fdn Pisana Sci, AIRC Start Unit, Canc Pharmacol Lab, Pisa, Italy
[12] Locat Univ Amsterdam, Dept Med Oncol, Amsterdam UMC, Amsterdam, Netherlands
关键词
MACROPHAGE INHIBITORY CYTOKINE-1; PROGNOSTIC BIOMARKERS; EMPIRICAL-EVIDENCE; SERUM; MARKERS; PLASMA; OSTEOPONTIN; BIAS; EXPRESSION; REGRESSION;
D O I
10.1016/j.eclinm.2022.101747
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background Novel 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. Methods PubMed, 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. Findings Aggregate 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. Interpretation Novel 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. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.
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页数:13
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