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.
