Non-invasive lung cancer diagnosis and prognosis based on multi-analyte liquid biopsy

In this study, we developed a set of experimental and computational tools to measure both genetic and epigenetic signals from plasma cfDNA of LC patients as well as patients bearing benign lung nodules (BLN) using high-throughput sequencing [3], aiming to explore the potential utility of blood-based biomarkers for LC diagnosis and prognosis. SEE PDF] Since some variants might derive from clonal hematopoiesis (CH) and confound the mutational analysis [4], genomic DNA (gDNA) of white blood cell (WBC) from cfDNA mutation-positive participants was also sequenced. Among WBC-shared cfDNA variants, the most frequently mutated genes included TP53, CBL, APOB, and CSMD3 for LC plasma, and CBL, CSMD3, and STAT3 for BLN plasma (Supplementary Fig. 6). [...]allele frequencies (AFs) of variants shared by cfDNA and matched WBC samples were highly correlated (Fig. 1b), suggesting that these mutations indeed originated from WBC and should be removed for downstream analysis [5]. Gene ontology (GO) annotations revealed that the 293 hyper DMRs were significantly enriched for genes encoding DNA-binding domains and homeobox domains, as well as genes involved in the developmental and transcriptional regulation process (Fig. 2c).