GRAIL, Inc., Menlo Park, CA, USA.
Nat Commun. 2021 Apr 21;12(1):2357. doi: 10.1038/s41467-021-22444-1.
Cell-free RNA (cfRNA) is a promising analyte for cancer detection. However, a comprehensive assessment of cfRNA in individuals with and without cancer has not been conducted. We perform the first transcriptome-wide characterization of cfRNA in cancer (stage III breast [n = 46], lung [n = 30]) and non-cancer (n = 89) participants from the Circulating Cell-free Genome Atlas (NCT02889978). Of 57,820 annotated genes, 39,564 (68%) are not detected in cfRNA from non-cancer individuals. Within these low-noise regions, we identify tissue- and cancer-specific genes, defined as "dark channel biomarker" (DCB) genes, that are recurrently detected in individuals with cancer. DCB levels in plasma correlate with tumor shedding rate and RNA expression in matched tissue, suggesting that DCBs with high expression in tumor tissue could enhance cancer detection in patients with low levels of circulating tumor DNA. Overall, cfRNA provides a unique opportunity to detect cancer, predict the tumor tissue of origin, and determine the cancer subtype.
无细胞 RNA (cfRNA) 是一种很有前途的癌症检测分析物。然而，尚未对癌症患者和非癌症患者的 cfRNA 进行全面评估。我们对来自 Circulating Cell-free Genome Atlas (NCT02889978) 的癌症（III 期乳腺癌[n=46]，肺癌[n=30]）和非癌症（n=89）参与者的 cfRNA 进行了首次全转录组特征分析。在 57820 个注释基因中，有 39564 个（68%）未在非癌症个体的 cfRNA 中检测到。在这些低噪声区域内，我们鉴定出组织和癌症特异性基因，这些基因被定义为“暗通道生物标志物”（DCB）基因，在癌症患者中反复检测到。血浆中的 DCB 水平与肿瘤脱落率和匹配组织中的 RNA 表达相关，表明在肿瘤组织中高表达的 DCB 可以提高低循环肿瘤 DNA 水平患者的癌症检测能力。总体而言，cfRNA 为检测癌症、预测肿瘤组织来源和确定癌症亚型提供了独特的机会。
