PT Unknown
AU Metzenmacher Dr., M
   Váraljai Dr., R
   Hegedüs Dr., B
   Cima Dr., I
   Forster Dr., J
   Schramm Dr., A
   Scheffler Dr., B
   Horn Dr., P
   Klein Dr., C
   Szarvas Dr., T
   Reis Dr., H
   Bielefeld, N
   Roesch Dr., A
   Aigner Dr., C
   Kunzmann Dr., V
   Wiesweg Dr., M
   Siveke Dr., J
   Schuler Dr., M
   Lueong Dr., S
TI Plasma Next Generation Sequencing and Droplet Digital-qPCR-Based Quantification of Circulating Cell-Free RNA for Noninvasive Early Detection of Cancer
PD 02
PY 2020
DI 10.3390/cancers12020353
LA en
DE liquid biopsy; cfRNA; cancer; ddPCR; NGS; POU6F2-AS2; early detection
AB 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.
ER