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A multi-analyte panel consisting of extracellular vesicle miRNAs and mRNAs, cfDNA, and CA19-9 shows utility for diagnosis and staging of pancreatic adenocarcinoma
- Source :
- Clin Cancer Res
- Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Oncology
Adult
Male
Cancer Research
medicine.medical_specialty
Pancreatic disease
endocrine system diseases
CA-19-9 Antigen
Adenocarcinoma
medicine.disease_cause
Article
Metastasis
Machine Learning
Proto-Oncogene Proteins p21(ras)
03 medical and health sciences
Extracellular Vesicles
0302 clinical medicine
Internal medicine
medicine
Biomarkers, Tumor
Humans
Digital polymerase chain reaction
RNA, Messenger
Liquid biopsy
Aged
Neoplasm Staging
Aged, 80 and over
business.industry
Liquid Biopsy
Computational Biology
Extracellular vesicle
Middle Aged
medicine.disease
digestive system diseases
Pancreatic Neoplasms
MicroRNAs
030104 developmental biology
ROC Curve
030220 oncology & carcinogenesis
Mutation
Biomarker (medicine)
CA19-9
Female
KRAS
business
Cell-Free Nucleic Acids
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Clin Cancer Res
- Accession number :
- edsair.doi.dedup.....35066a9ac14c07c0b0ff7f594356c5a4