Metzenmacher Martin, Váraljai Renáta, Hegedüs Balazs, Cima Igor, Forster Jan, Schramm Alexander, Scheffler Björn, Horn Peter A, Klein Christoph A, Szarvas Tibor, Reis Hennig, Bielefeld Nicola, Roesch Alexander, Aigner Clemens, Kunzmann Volker, Wiesweg Marcel, Siveke Jens T, Schuler Martin, Lueong Smiths S
Department of Medical Oncology, West German Cancer Center, University Hospital Essen, University Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany.
Division of Thoracic Oncology, University Medicine Essen-Ruhrlandklinik, University Duisburg-Essen, Tüschener Weg 40, 45239 Essen, Germany.
Cancers (Basel). 2020 Feb 4;12(2):353. doi: 10.3390/cancers12020353.
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 ( = 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 ( = 0.044). In summary, our findings support further validation of cfRNA detection by RT-ddPCR as a biomarker for early detection of solid cancers.
癌症的早期检测对于降低癌症相关死亡率具有很大的前景。循环肿瘤特异性核酸的检测具有一定前景，但当前技术仍存在灵敏度和特异性问题。我们通过下一代测序（NGS）和实时液滴数字PCR（RT-ddPCR）研究了非小细胞肺癌（NSCLC；56例IV期，39例I-III期）、胰腺癌（PDAC，20例III期）、恶性黑色素瘤（MM，12例III-IV期）、尿路上皮膀胱癌（UBC，22例II期和IV期）患者以及65名健康对照者的游离RNA（cfRNA）。我们通过NGS在NSCLC和PDAC中鉴定出192个重叠的上调转录本，其中90%以上为非编码转录本。鉴定出了先前报道的转录本（如HOTAIRM1）。POU6F2-AS2的血浆cfRNA转录水平可将NSCLC患者与健康供体区分开来（IV期和I-III期的AUC分别为0.82和0.76），并且与已确立的肿瘤标志物细胞角蛋白19片段（Cyfra 21-1）显著相关（P = 0.017）。cfRNA产量和POU6F2-AS转录本丰度可将PDAC患者与健康供体区分开来（AUC = 1.0）。POU-6F2-AS2转录本在MM中显著更高（P = 0.044）。总之，我们的研究结果支持进一步验证通过RT-ddPCR检测cfRNA作为实体癌早期检测生物标志物的可行性。
