Independent transcriptional patterns reveal biological processes associated with disease-free survival in early colorectal cancer

Abstract

Abstract Bulk transcriptional profiles of early colorectal cancer (CRC) can fail to detect biological processes associated with disease-free survival (DFS) if the transcriptional patterns are subtle and/or obscured by other processes’ patterns. Consensus independent component analysis (c-ICA) can dissect such transcriptomes into statistically independent transcriptional components (TCs), capturing both pronounced and subtle biological processes. Here, we applied c-ICA to 4,268 transcriptomes and identified 191 TCs, 43 of which were associated with DFS, revealing transcriptional diversity among DFS-associated biological processes. A prominent example is the epithelial-mesenchymal transition (EMT), for which we identified an association with eight independent DFS-associated TCs, each with coordinated upregulation or downregulation of various sets of genes. This finding indicates that early CRC may have eight distinct routes to achieve EMT, each requiring a specific peri-operative treatment strategy. Finally, we stratified patients into DFS patient subgroups with distinct transcriptional patterns associated with stage 2 and stage 3 CRC.