Integrative proteomic analysis reveals potential high-frequency alternative open reading frame-encoded peptides in human colorectal cancer.

Identification of alternative open reading frame-encoded peptides (AEPs) for the diagnosis of colorectal cancer at the proteome level is largely unexplored because of a lack of comprehensive proteomics data. Here, we performed a comprehensive integrative analysis of mass spectral data published by Clinical Proteomic Tumor Analysis Consortium and characterized 93 high-confident AEPs encoded within 75 genes. There are four cancer-related genes appeared to have AEPs identified frequently in >20 out of 95 colorectal cancer samples, including ABCF2, AR, RBM10 and NRG1. Further network analysis of the identified AEPs found the enrichment of novel AEPs within hormone androgen receptor and a highly-modularised network with 42 genes associated with patient survival. Our results not only suggested a mechanistic view of how AEPs work in cancer progression, but also shed light on somatic amino acid mutations in AEPs, which might be overlooked previously because of their low frequencies. In particular, potential high-frequency mutations in 77 samples associated with EDARADD may contribute to the discovery of new biomarkers and the development of innovative therapeutic approaches.