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

GND
1095893955
ORCID
0000-0001-5395-9010
Affiliation
Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany, Martin.Metzenmacher@uk-essen.de
Metzenmacher, Martin;
GND
1200553365
ORCID
0000-0001-6852-6859
Affiliation
Department of Dermatology, University Hospital Essen, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany, Renata.Varaljai@uk-essen.de
Váraljai, Renáta;
GND
1217799648
ORCID
0000-0002-4341-4153
Affiliation
Department of Thoracic Surgery, Ruhrlandklinik, University Duisburg-Essen, D-45239 Essen, Germany, Balazs.Hegedues@rlk.uk-essen.de
Hegedüs, Balazs;
Affiliation
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany, i.cima@dkfz-heidelberg.de
Cima, Igor;
Affiliation
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany, j.forster@dkfz-heidelberg.de
Forster, Jan;
GND
120872729X
ORCID
0000-0001-7670-7529
Affiliation
Laboratory for Molecular Oncology, Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany, alexander.schramm@uni-due.de
Schramm, Alexander;
GND
121203271
VIAF
25453077
ORCID
0000-0001-8316-6556
Affiliation
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany, Bjoern.Scheffler@uk-essen.de
Scheffler, Björn;
GND
121495736
LSF
14381
Affiliation
Institute for Transfusion Medicine, University Hospital Essen, 45122 Essen, Germany, Peter.Horn@uk-essen.de
Horn, Peter A.;
GND
1026455901
Affiliation
Experimental Medicine and Therapy Research, University of Regensburg, 93053 Regensburg, Germany, Christoph.Klein@klinik.uni-regensburg.de
Klein, Christoph;
GND
1017203822
LSF
51486
Affiliation
Department of Urology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, 45122 Essen, Germany, Tibor.Szarvas@uk-essen.de
Szarvas, Tibor;
GND
140588655
ORCID
0000-0003-1373-5295
LSF
60023
Affiliation
Institute of Pathology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, 45147 Essen, Germany, Henning.Reis@uk-essen.de
Reis, Henning;
GND
1217808957
Affiliation
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany, Nicola.Bielefeld@uk-essen.de
Bielefeld, Nicola;
GND
123022304
LSF
56143
Affiliation
Department of Dermatology, University Hospital Essen, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany, Alexander.Roesch@uk-essen.de
Rösch, Alexander;
GND
1079361375
ORCID
0000-0002-7787-991X
LSF
58964
Affiliation
Department of Thoracic Surgery, Ruhrlandklinik, University Duisburg-Essen, D-45239 Essen, Germany, Clemens.Aigner@rlk.uk-essen.de
Aigner, Clemens;
Affiliation
Department of Internal Medicine II, University Hospital Würzburg, 97080 Würzburg, Germany, kunzmann_v@ukw.de
Kunzmann, Volker;
GND
1053769695
LSF
60127
Affiliation
Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany, Marcel.Wiesweg@uk-essen.de
Wiesweg, Marcel;
GND
123603498
ORCID
0000-0002-8772-4778
LSF
59282
Affiliation
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany, Jens.Siveke@uk-essen.de
Siveke, Jens T.;
GND
1210889617
LSF
49485
Affiliation
Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany, Martin.Schuler@uk-essen.de
Schuler, Martin;
GND
1061065030
ORCID
0000-0002-2776-6706
Affiliation
German Cancer Consortium (DKTK), Partner site University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany, smiths-sengkwawoh.lueong@uk-essen.de
Lueong, Smiths S.

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.

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Citation style:
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., 2020. Plasma Next Generation Sequencing and Droplet Digital-qPCR-Based Quantification of Circulating Cell-Free RNA for Noninvasive Early Detection of Cancer. https://doi.org/10.3390/cancers12020353
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