TY  - JOUR
A1  - Metzenmacher, Martin
A1  - Váraljai, Renáta
A1  - Hegedüs, Balazs
A1  - Cima, Igor
A1  - Forster, Jan
A1  - Schramm, Alexander
A1  - Scheffler, Björn
A1  - Horn, Peter A.
A1  - Klein, Christoph A.
A1  - Szarvas, Tibor
A1  - Reis, Hennig
A1  - Bielefeld, Nicola
A1  - Roesch, Alexander
A1  - Aigner, Clemens
A1  - Kunzmann, Volker
A1  - Wiesweg, Marcel
A1  - Siveke, Jens T.
A1  - Schuler, Martin
A1  - Lueong, Smiths S.
T1  - Plasma Next Generation Sequencing and Droplet Digital-qPCR-Based Quantification of Circulating Cell-Free RNA for Noninvasive Early Detection of Cancer
JF  - Cancers
N2  - 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.
KW  - liquid biopsy
KW  - cfRNA
KW  - cancer
KW  - ddPCR
KW  - NGS
KW  - POU6F2-AS2
KW  - early detection
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200553
SN  - 2072-6694
VL  - 12
IS  - 2
ER  - 
TY  - JOUR
A1  - Hagemann, Carsten
A1  - Neuhaus, Nikolas
A1  - Dahlmann, Mathias
A1  - Kessler, Almuth F.
A1  - Kobelt, Dennis
A1  - Herrmann, Pia
A1  - Eyrich, Matthias
A1  - Freitag, Benjamin
A1  - Linsenmann, Thomas
A1  - Monoranu, Camelia M.
A1  - Ernestus, Ralf-Ingo
A1  - Löhr, Mario
A1  - Stein, Ulrike
T1  - Circulating MACC1 transcripts in glioblastoma patients predict prognosis and treatment response
JF  - Cancers
N2  - Glioblastoma multiforme is the most aggressive primary brain tumor of adults, but lacksreliable and liquid biomarkers. We evaluated circulating plasma transcripts of metastasis-associatedin colon cancer-1 (MACC1), a prognostic biomarker for solid cancer entities, for prediction of clinicaloutcome and therapy response in glioblastomas.  MACC1 transcripts were significantly higher inpatients compared to controls.  Low MACC1 levels clustered together with other prognosticallyfavorable markers.  It was associated with patients’ prognosis in conjunction with the isocitratedehydrogenase (IDH) mutation status: IDH1 R132H mutation and low MACC1 was most favorable(median overall survival (OS) not yet reached), IDH1 wildtype and high MACC1 was worst (medianOS 8.1 months), while IDH1 wildtype and low MACC1 was intermediate (median OS 9.1 months).No patients displayed IDH1 R132H mutation and high MACC1. Patients with low MACC1 levelsreceiving standard therapy survived longer (median OS 22.6 months) than patients with high MACC1levels (median OS 8.1 months).   Patients not receiving the standard regimen showed the worstprognosis, independent of MACC1 levels (low: 6.8 months, high: 4.4 months). Addition of circulatingMACC1 transcript levels to the existing prognostic workup may improve the accuracy of outcomeprediction and help define more precise risk categories of glioblastoma patients.
KW  - metastasis-associated in colon cancer 1 (MACC1)
KW  - glioblastoma multiforme
KW  - liquid biopsy
KW  - therapy response
KW  - prognostic marker
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197327
SN  - 2072-6694
VL  - 11
IS  - 6
ER  -