Integrated multi-omics approach to distinct molecular characterization and classification of early-onset colorectal cancer

Cell Rep Med. 2023 Mar 21;4(3):100974. doi: 10.1016/j.xcrm.2023.100974. Epub 2023 Mar 14.


Incidence of early-onset colorectal cancer (EOCRC), defined by a diagnosed age under 50 years, is increasing, but its heterogeneous etiologies that differ from general CRC remain undetermined. We initially characterize the genome, epigenome, transcriptome, and proteome of tumors from 79 patients in a Chinese CRC cohort. Data for an additional 126 EOCRC subjects are obtained from the International Cancer Genome Consortium Chinese cohort and The Cancer Genome Atlas European cohort. We observe that early-onset tumors have a high tumor mutation burden; increased DNA repair features by mutational signature 3 and multi-layer pathway enrichments; strong perturbations at effects of DNA methylation and somatic copy-number alteration on gene expression; and upregulated immune infiltration as hot tumors underlying immunophenotypes. Notably, LMTK3 exhibits ancestral mutation disparity, potentially being a functional modulator and biomarker that drives molecular alterations in EOCRC development and immunotherapies. This integrative omics study provides valuable knowledge for precision oncology of CRC.

Keywords: LMTK3; early-onset colorectal cancer; immunophenotype; multi-omics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Humans
  • Membrane Proteins / genetics
  • Middle Aged
  • Multiomics*
  • Mutation
  • Precision Medicine
  • Protein Serine-Threonine Kinases / genetics
  • Transcriptome / genetics


  • LMTK3 protein, human
  • Membrane Proteins
  • Protein Serine-Threonine Kinases