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Clin Cancer Res ; 26(13): 3248-3258, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32299821

RESUMO

PURPOSE: To determine whether a multianalyte liquid biopsy can improve the detection and staging of pancreatic ductal 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 extracellular vesicle 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 measured by qPCR, ccfDNA KRAS G12D/V/R mutations detected by droplet digital PCR, and CA19-9 measured by electrochemiluminescence immunoassay. We applied machine learning to training sets and subsequently evaluated model performance in independent, user-blinded test sets. RESULTS: To identify patients with PDAC versus those without, we generated a classification model using a training set of 47 subjects (20 PDAC and 27 noncancer). When applied to a blinded test set (N = 136), the model achieved an AUC of 0.95 and accuracy of 92%, superior to the best individual biomarker, CA19-9 (89%). We next used a cohort of 20 patients with PDAC to train our model for disease staging and applied it to a blinded test set of 25 patients clinically staged by imaging as metastasis-free, including 9 subsequently determined to have had occult metastasis. Our workflow achieved significantly higher accuracy for disease staging (84%) than imaging alone (accuracy = 64%; P < 0.05). CONCLUSIONS: Algorithmically combining blood-based biomarkers may improve PDAC diagnostic accuracy and preoperative identification of nonmetastatic patients best suited for surgery, although larger validation studies are necessary.


Assuntos
Adenocarcinoma/diagnóstico , Adenocarcinoma/metabolismo , Biomarcadores Tumorais , Vesículas Extracelulares/metabolismo , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/metabolismo , Adenocarcinoma/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno CA-19-9 , Ácidos Nucleicos Livres , Biologia Computacional/métodos , Feminino , Humanos , Biópsia Líquida/métodos , Aprendizado de Máquina , Masculino , MicroRNAs , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Neoplasias Pancreáticas/etiologia , Proteínas Proto-Oncogênicas p21(ras)/genética , RNA Mensageiro , Curva ROC
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