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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- 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 generationEarly 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.…
Autor(en): | Martin Metzenmacher, Renáta Váraljai, Balazs Hegedüs, Igor Cima, Jan Forster, Alexander Schramm, Björn Scheffler, Peter A. Horn, Christoph A. Klein, Tibor Szarvas, Hennig Reis, Nicola Bielefeld, Alexander Roesch, Clemens Aigner, Volker Kunzmann, Marcel Wiesweg, Jens T. Siveke, Martin Schuler, Smiths S. Lueong |
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URN: | urn:nbn:de:bvb:20-opus-200553 |
Dokumentart: | Artikel / Aufsatz in einer Zeitschrift |
Institute der Universität: | Medizinische Fakultät / Medizinische Klinik und Poliklinik II |
Sprache der Veröffentlichung: | Englisch |
Titel des übergeordneten Werkes / der Zeitschrift (Englisch): | Cancers |
ISSN: | 2072-6694 |
Erscheinungsjahr: | 2020 |
Band / Jahrgang: | 12 |
Heft / Ausgabe: | 2 |
Originalveröffentlichung / Quelle: | Cancers 2020, 12(2), 353; https://doi.org/10.3390/cancers12020353 |
DOI: | https://doi.org/10.3390/cancers12020353 |
Allgemeine fachliche Zuordnung (DDC-Klassifikation): | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Freie Schlagwort(e): | NGS; POU6F2-AS2; cancer; cfRNA; ddPCR; early detection; liquid biopsy |
Datum der Freischaltung: | 31.08.2020 |
Datum der Erstveröffentlichung: | 04.02.2020 |
EU-Projektnummer / Contract (GA) number: | 641458 |
OpenAIRE: | OpenAIRE |
Lizenz (Deutsch): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |