Cell-free multi-omics analysis reveals potential biomarkers in gastrointestinal cancer patients’ blood
Yuhuan Tao, Shaozhen Xing, Shuai Zuo, Pengfei Bao, Yunfan Jin, Yu Li, Mingyang Li, Yingchao Wu, Shanwen Chen, Xiaojuan Wang, Yumin Zhu, Ying Feng, Xiaohua Douglas Zhang, Xianbo Wang, Qiaoran Xi, Qian Lu, Pengyuan Wang, Zhi John Lu
Abstract
During cancer progression, tumorigenic and immune signals are spread through circulating molecules, such as cell-free DNA (cfDNA) and cell-free RNA (cfRNA) in the blood. So far, they have not been comprehensively investigated in gastrointestinal cancers. Here, we profile 4 categories of cell-free omics data from patients with colorectal cancer and patients with stomach adenocarcinoma and then assay 15 types of genomic, epigenomic, and transcriptomic variations. We find that multi-omics data are more appropriate for detection of cancer genes compared with single-omics data. In particular, cfRNAs are more sensitive and informative than cfDNAs in terms of detection rate, enriched functional pathways, etc. Moreover, we identify several peripheral immune signatures that are suppressed in patients with cancer. Specifically, we establish a γδ-T cell score and a cancer-associated-fibroblast (CAF) score, providing insights into clinical statuses like cancer stage and survival. Overall, we reveal a cell-free multi-molecular landscape that is useful for blood monitoring in personalized cancer treatment.