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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
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Raf kinase inhibitory protein role in the molecular subtyping of breast cancer

Fahd Al-Mulla1, Makia Marafie, Tuan Zea Tan

  • 1Department of Pathology, Faculty of Medicine, Kuwait University Health Sciences Centre, Safat, 13110, Kuwait.

Journal of Cellular Biochemistry
|October 15, 2013
PubMed

Insights

Reduced RKIP expression is linked to poorer recurrence-free survival in breast cancer patients. RKIP levels vary significantly across molecular subtypes, particularly impacting Luminal A breast cancer prognosis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Bioinformatics

Background:

  • Breast cancer comprises diverse molecular subtypes with distinct clinical behaviors.
  • Identifying reliable biomarkers for prognosis and subclassification is crucial for personalized treatment strategies.
  • Raf kinase inhibitor protein (RKIP) has emerged as a potential player in cancer progression.

Purpose of the Study:

  • To investigate the association between RKIP expression and breast cancer molecular subtypes.
  • To evaluate the prognostic value of RKIP expression in relation to recurrence-free survival (RFS).
  • To determine if RKIP expression can refine the molecular subclassification of breast cancer.

Main Methods:

  • Analysis of microarray gene expression data from 2,333 human breast cancer samples across 26 cohorts.
  • Molecular subtyping using single-sample Gene Set Enrichment Analysis.
  • Statistical analysis including Log-rank tests, Kaplan-Meier curves, and Cox proportional-hazards models for RFS and prognostic value.

Main Results:

  • Loss or reduced RKIP expression was significantly associated with decreased RFS, independent of lymph node metastasis.
  • Basal-like, Claudin-low, and Her-2-enriched subtypes showed significantly lower RKIP levels.
  • Luminal subtypes (A and B) exhibited the highest RKIP expression; RKIP was prognostic in ER+ and ER- subgroups.
  • RKIP expression was particularly valuable in distinguishing survival outcomes within the Luminal A subtype, especially in lymph node-negative cases.

Conclusions:

  • RKIP expression levels are significantly correlated with molecular subtypes of breast cancer.
  • RKIP expression serves as an independent prognostic marker for recurrence-free survival.
  • RKIP expression enhances the prognostic value of molecular subclassification, especially for Luminal A breast cancer.
Keywords:
AGGRESSIVE CANCERBASALBREAST CANCERCLAUDIN-LOWDISEASE-FREE SURVIVALERBB2ERKESTROGEN RECEPTORLUMINAL APEBP1PROGNOSISRKIP

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