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Open AccessArticle

Plasma Next Generation Sequencing and Droplet Digital-qPCR-Based Quantification of Circulating Cell-Free RNA for Noninvasive Early Detection of Cancer

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Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany
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Division of Thoracic Oncology, University Medicine Essen-Ruhrlandklinik, University Duisburg-Essen, Tüschener Weg 40, 45239 Essen, Germany
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Department of Dermatology, University Hospital Essen, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany
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German Cancer Consortium (DKTK), Partner site University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany
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Department of Thoracic Surgery, Ruhrlandklinik, University Duisburg-Essen, D-45239 Essen, Germany
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DKFZ-Division Translational Neurooncology at the WTZ, DKTK partner site, University Hospital Essen, 45122 Essen, Germany
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Chair for Genome Informatics, Department of Human Genetics, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany
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Laboratory for Molecular Oncology, Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany
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Institute for Transfusion Medicine, University Hospital Essen, 45122 Essen, Germany
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Experimental Medicine and Therapy Research, University of Regensburg, 93053 Regensburg, Germany
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Fraunhofer-Institute for Toxicology and Experimental Medicine, Division of Personalized Tumour Therapy, 93053 Regensburg, Germany
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Department of Urology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany
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Department of Urology, Semmelweis University, H-1085 Budapest, Hungary
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Institute of Pathology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany
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Institute for Developmental Cancer Therapeutics, West German Cancer Center, University Hospital Essen, 45122 Essen, Germany
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Department of Internal Medicine II, University Hospital Würzburg, 97080 Würzburg, Germany
*
Author to whom correspondence should be addressed.
Cancers 2020, 12(2), 353; https://doi.org/10.3390/cancers12020353
Received: 27 December 2019 / Revised: 29 January 2020 / Accepted: 31 January 2020 / Published: 4 February 2020
(This article belongs to the Collection Cancer Biomarkers)
Early detection of cancer holds high promise for reducing cancer-related mortality. Detection of circulating tumor-specific nucleic acids holds promise, but sensitivity and specificity issues remain with current technology. We studied cell-free RNA (cfRNA) in patients with non-small cell lung cancer (NSCLC; n = 56 stage IV, n = 39 stages I-III), pancreatic cancer (PDAC, n = 20 stage III), malignant melanoma (MM, n = 12 stage III-IV), urothelial bladder cancer (UBC, n = 22 stage II and IV), and 65 healthy controls by means of next generation sequencing (NGS) and real-time droplet digital PCR (RT-ddPCR). We identified 192 overlapping upregulated transcripts in NSCLC and PDAC by NGS, more than 90% of which were noncoding. Previously reported transcripts (e.g., HOTAIRM1) were identified. Plasma cfRNA transcript levels of POU6F2-AS2 discriminated NSCLC from healthy donors (AUC = 0.82 and 0.76 for stages IV and I–III, respectively) and significantly associated (p = 0.017) with the established tumor marker Cyfra 21-1. cfRNA yield and POU6F2-AS transcript abundance discriminated PDAC patients from healthy donors (AUC = 1.0). POU6F2-AS2 transcript was significantly higher in MM (p = 0.044). In summary, our findings support further validation of cfRNA detection by RT-ddPCR as a biomarker for early detection of solid cancers. View Full-Text
Keywords: liquid biopsy; cfRNA; cancer; ddPCR; NGS; POU6F2-AS2; early detection liquid biopsy; cfRNA; cancer; ddPCR; NGS; POU6F2-AS2; early detection
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Metzenmacher, M.; Váraljai, R.; Hegedüs, B.; Cima, I.; Forster, J.; Schramm, A.; Scheffler, B.; Horn, P.A.; Klein, C.A.; Szarvas, T.; Reis, H.; Bielefeld, N.; Roesch, A.; Aigner, C.; Kunzmann, V.; Wiesweg, M.; Siveke, J.T.; Schuler, M.; Lueong, S.S. Plasma Next Generation Sequencing and Droplet Digital-qPCR-Based Quantification of Circulating Cell-Free RNA for Noninvasive Early Detection of Cancer. Cancers 2020, 12, 353.

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