Panomics reveals patient individuality as the major driver of colorectal cancer progression

J Transl Med. 2023 Jan 23;21(1):41. doi: 10.1186/s12967-022-03855-0.

Abstract

Background: Colorectal cancer (CRC) is one of the most prevalent cancers, with over one million new cases per year. Overall, prognosis of CRC largely depends on the disease stage and metastatic status. As precision oncology for patients with CRC continues to improve, this study aimed to integrate genomic, transcriptomic, and proteomic analyses to identify significant differences in expression during CRC progression using a unique set of paired patient samples while considering tumour heterogeneity.

Methods: We analysed fresh-frozen tissue samples prepared under strict cryogenic conditions of matched healthy colon mucosa, colorectal carcinoma, and liver metastasis from the same patients. Somatic mutations of known cancer-related genes were analysed using Illumina's TruSeq Amplicon Cancer Panel; the transcriptome was assessed comprehensively using Clariom D microarrays. The global proteome was evaluated by liquid chromatography-coupled mass spectrometry (LC‒MS/MS) and validated by two-dimensional difference in-gel electrophoresis. Subsequent unsupervised principal component clustering, statistical comparisons, and gene set enrichment analyses were calculated based on differential expression results.

Results: Although panomics revealed low RNA and protein expression of CA1, CLCA1, MATN2, AHCYL2, and FCGBP in malignant tissues compared to healthy colon mucosa, no differentially expressed RNA or protein targets were detected between tumour and metastatic tissues. Subsequent intra-patient comparisons revealed highly specific expression differences (e.g., SRSF3, OLFM4, and CEACAM5) associated with patient-specific transcriptomes and proteomes.

Conclusion: Our research results highlight the importance of inter- and intra-tumour heterogeneity as well as individual, patient-paired evaluations for clinical studies. In addition to changes among groups reflecting CRC progression, we identified significant expression differences between normal colon mucosa, primary tumour, and liver metastasis samples from individuals, which might accelerate implementation of precision oncology in the future.

Keywords: Biomarkers; Colorectal cancer; Metastasis; Panomics; Patient individuality; Tumour heterogeneity.

MeSH terms

  • Biomarkers, Tumor
  • Chromatography, Liquid
  • Colorectal Neoplasms* / genetics
  • Humans
  • Liver Neoplasms* / genetics
  • Precision Medicine
  • Proteomics / methods
  • RNA
  • Serine-Arginine Splicing Factors
  • Tandem Mass Spectrometry

Substances

  • RNA
  • Biomarkers, Tumor
  • SRSF3 protein, human
  • Serine-Arginine Splicing Factors