The cytoplasmic expression of FSTL3 correlates with colorectal cancer progression, metastasis status and prognosis

J Cell Mol Med. 2023 Mar;27(5):672-686. doi: 10.1111/jcmm.17690. Epub 2023 Feb 18.

Abstract

Follistatin-like (FSTL) family members are associated with cancer progression. However, differences between FSTL members with identical cancer types have not been systematically investigated. Among the most malignant tumours worldwide, colorectal cancer (CRC) has high metastatic potential and chemoresistance, which makes it challenging to treat. A systematic examination of the relationship between the expression of FSTL family members in CRC will provide valuable information for prognosis and therapeutic development. Based on large cohort survival analyses, we determined that FSTL3 was associated with a significantly worse prognosis in CRC at the RNA and protein levels. Immunohistochemistry staining of CRC specimens revealed that FSTL3 expression levels in the cytosol were significantly associated with a poor prognosis in terms of overall and disease-free survival. Molecular simulation analysis showed that FSTL3 participated in multiple cell motility signalling pathways via the TGF-β1/TWIST1 axis to control CRC metastasis. The findings provide evidence of the significance of FSTL3 in the oncogenesis and metastasis of CRC. FSTL3 may be useful as a diagnostic or prognostic biomarker, and as a potential therapeutic target.

Keywords: FSTL3; bioinformatics; colorectal cancer; follistatin-like; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics
  • Cell Transformation, Neoplastic
  • Cohort Studies
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / pathology
  • Cytosol / metabolism
  • Follistatin-Related Proteins* / genetics
  • Follistatin-Related Proteins* / metabolism
  • Humans
  • Signal Transduction

Substances

  • Biomarkers, Tumor
  • Fstl3 protein, human
  • Follistatin-Related Proteins