Tissue Elasticity as a Diagnostic Marker of Molecular Mutations in Morphologically Heterogeneous Colorectal Cancer

Int J Mol Sci. 2024 May 14;25(10):5337. doi: 10.3390/ijms25105337.

Abstract

The presence of molecular mutations in colorectal cancer (CRC) is a decisive factor in selecting the most effective first-line therapy. However, molecular analysis is routinely performed only in a limited number of patients with remote metastases. We propose to use tissue stiffness as a marker of the presence of molecular mutations in CRC samples. For this purpose, we applied compression optical coherence elastography (C-OCE) to calculate stiffness values in regions corresponding to specific CRC morphological patterns (n = 54). In parallel to estimating stiffness, molecular analysis from the same zones was performed to establish their relationships. As a result, a high correlation between the presence of KRAS/NRAS/BRAF driver mutations and high stiffness values was revealed regardless of CRC morphological pattern type. Further, we proposed threshold stiffness values for label-free targeted detection of molecular alterations in CRC tissues: for KRAS, NRAS, or BRAF driver mutation-above 803 kPa (sensitivity-91%; specificity-80%; diagnostic accuracy-85%), and only for KRAS driver mutation-above 850 kPa (sensitivity-90%; specificity-88%; diagnostic accuracy-89%). To conclude, C-OCE estimation of tissue stiffness can be used as a clinical diagnostic tool for preliminary screening of genetic burden in CRC tissues.

Keywords: colorectal cancer; compression optical coherence elastography; driver mutation; molecular analysis; morphological patterns; tissue stiffness.

MeSH terms

  • Aged
  • Biomarkers, Tumor* / genetics
  • Colorectal Neoplasms* / diagnosis
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Elasticity
  • Elasticity Imaging Techniques* / methods
  • Female
  • GTP Phosphohydrolases* / genetics
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Mutation*
  • Proto-Oncogene Proteins B-raf* / genetics
  • Proto-Oncogene Proteins p21(ras)* / genetics

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)
  • BRAF protein, human
  • GTP Phosphohydrolases
  • KRAS protein, human
  • NRAS protein, human
  • Membrane Proteins