Cell-free multi-omics analysis reveals tumor status-informative signatures in gastrointestinal cancer patients’ plasma

Abstract

AbstractDuring cancer development, host’s tumorigenesis and immune signals are released to and informed by circulating molecules, like cell-free DNA (cfDNA) and RNA (cfRNA) in blood. However, these two kinds of molecules are still not systematically compared in gastrointestinal cancer. Here, we profiled 4 types of cell-free omics data from colorectal and stomach cancer patients, and assayed 15 types of genomic, epi-genomic, and transcriptomic variations. First, we demonstrated that the multi-omics data were more capable of detecting cancer genes than the single-omics data, where cfRNAs were more sensitive and informative than cfDNAs in terms of detection ratio, variation type, altered number, and enriched functional pathway. Moreover, we revealed several peripheral immune signatures that were suppressed in cancer patients and originated from specific circulating and tumor-microenvironment cells. Particularly, we defined a γδ-T-cell score and a cancer-associated-fibroblast (CAF) score using the cfRNA-seq data of 143 cancer patients. They were informative of clinical status like cancer stage, tumor size, and survival. In summary, our work reveals the cell-free multi-molecular landscape of colorectal and stomach cancer, and provides a potential monitoring utility in blood for the personalized cancer treatment.