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Protein Tyrosine Kinase 7 (PTK7) in Breast Cancer: A Retrospective Analysis of Tumour Expression and Association with

Kate Lacey1, Megan R Greener1, Tangkam R Marak1

  • 1Nottingham Breast Cancer Research Centre, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK.

Cancers
|September 28, 2024
PubMed

Insights

Protein tyrosine kinase 7 (PTK7) expression impacts breast cancer survival. While protein levels showed no association, PTK7 mRNA levels correlated with improved survival in specific patient subgroups, highlighting its prognostic potential.

Area of Science:

  • Molecular Biology
  • Oncology
  • Biochemistry

Background:

  • Protein tyrosine kinase 7 (PTK7), also known as colon carcinoma kinase 4 (CCK4), is a catalytically inactive transmembrane receptor implicated in Wnt signaling pathways.
  • PTK7 is recognized as a potential therapeutic target, with an antibody-drug conjugate (cofetuzumab pelidotin) undergoing Phase I clinical trials for various cancers, including triple-negative breast cancer.

Purpose of the Study:

  • To investigate the association between PTK7 expression (both protein and mRNA) and clinicopathological features in early-stage invasive breast tumors.
  • To determine the prognostic significance of PTK7 expression in relation to breast cancer-specific survival.

Main Methods:

  • PTK7 protein expression was quantified in 1136 early-stage invasive breast tumors using immunohistochemistry.
  • PTK7 mRNA expression was analyzed in the METABRIC (n=1980) and TCGA (n=1082) breast cancer cohorts.
  • Statistical analyses were performed to correlate PTK7 expression levels with clinicopathological variables and patient survival outcomes, including stratification by Nottingham Prognostic Index (NPI).

Main Results:

  • No significant association was found between PTK7 protein expression levels and breast cancer-specific survival.
  • PTK7 mRNA expression in the METABRIC cohort demonstrated a significant association with improved breast cancer-specific survival (p < 0.001).
  • Both PTK7 protein and mRNA expression were linked to breast cancer-specific survival in patients with poor and moderate NPI scores, respectively.

Conclusions:

  • PTK7 expression, particularly at the mRNA level, serves as a potential prognostic biomarker in specific subgroups of breast cancer patients.
  • The differential association of PTK7 protein versus mRNA with survival suggests distinct roles or regulatory mechanisms influencing patient outcomes.
Keywords:
PTK7biomarkersbreast cancerprognosisprotein tyrosine kinase 7triple negative

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