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Frequent alterations of SLIT2-ROBO1-CDC42 signalling pathway in breast cancer: clinicopathological correlation

Rittwika Bhattacharya1, Nupur Mukherjee, Hemantika Dasgupta

  • 1Department of Oncogene Regulation, Chittaranjan National Cancer Institute, 37, S.P. Mukherjee Road, Kolkata 700 026, India.ckpanda.cnci@gmail.com.

Journal of Genetics
|September 24, 2016
PubMed

Insights

The SLIT2-ROBO1-CDC42 pathway is frequently altered in breast cancer, particularly in triple-negative breast cancer. Alterations in this pathway, along with reduced phospho-CDC42, predict poor patient survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The SLIT2-ROBO1/2-CDC42 signaling pathway plays a role in cell development.
  • Understanding its role in breast cancer (BC) is crucial for identifying new therapeutic targets.

Purpose of the Study:

  • To investigate the molecular alterations and clinical significance of the SLIT2-ROBO1/2-CDC42 pathway in primary breast cancer.
  • To correlate these alterations with breast cancer subtypes and patient survival.

Main Methods:

  • Analysis of deletion and methylation frequencies of SLIT2, ROBO1, ROBO2, and CDC42 genes in 150 primary breast cancer samples.
  • Immunohistochemical analysis to assess protein expression levels.
  • Correlation of molecular alterations with clinical data, including patient survival and breast cancer subtypes (e.g., triple-negative breast cancer [TNBC], HER2-enriched, luminal A).

Main Results:

  • Majority of tumors (80%) exhibited alterations in at least one gene of the pathway.
  • SLIT2 showed the highest frequency of alterations (75.3%), with significantly higher alterations observed in TNBC compared to HER2-enriched subtypes.
  • Coalterations in SLIT2 and/or ROBO1 were associated with reduced expression of phospho-Serine-71 CDC42 and predicted poor patient survival.

Conclusions:

  • The SLIT2-ROBO1-CDC42 signaling pathway is frequently dysregulated in breast cancer.
  • Alterations in this pathway, especially in SLIT2, are more common in TNBC.
  • The pathway's molecular alterations and reduced phospho-CDC42 expression serve as potential biomarkers for predicting breast cancer progression and patient outcomes.

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