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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-200553
  • 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.show moreshow less

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Metadaten
Author: 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
URN:urn:nbn:de:bvb:20-opus-200553
Document Type:Journal article
Faculties:Medizinische Fakultät / Medizinische Klinik und Poliklinik II
Language:English
Parent Title (English):Cancers
ISSN:2072-6694
Year of Completion:2020
Volume:12
Issue:2
Source:Cancers 2020, 12(2), 353; https://doi.org/10.3390/cancers12020353
DOI:https://doi.org/10.3390/cancers12020353
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:NGS; POU6F2-AS2; cancer; cfRNA; ddPCR; early detection; liquid biopsy
Release Date:2020/08/31
Date of first Publication:2020/02/04
EU-Project number / Contract (GA) number:641458
OpenAIRE:OpenAIRE
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International