title: Raf kinase inhibitory protein role in the molecular subtyping of breast cancer.
abstract: In this study, we examined the association between the RKIP expression and the molecular subtypes of breast cancer. Microarray gene expression data of 2,333 human breast cancer from 26 different cohorts performed on Affymetrix U133A or U133Plus2 platforms were downloaded from Array Express and Gene Expression Omnibus and the molecular subtype of breast cancer for the samples was determined by single sample Gene Set Enrichment Analysis. Differences in recurrence-free survival (RFS) were tested using the Log-rank test in univariate analysis and displayed using Kaplan-Meier curves. Cox proportional-hazards model was used to calculate the hazard ratio using univariate and multivariate analysis. Loss or reduced RKIP expression was associated with reduced RFS in breast cancer using univariate and multivariate analyses, which was independent of lymph node (LN) metastasis status. Basal-like, Claudin-low, and Her-2-enriched tumors had significantly lower RKIP levels compared to other subclasses (P < 0.0001). Conversely, the Luminal subclass exhibited the highest expression levels of RKIP (P < 0.0001 for Luminal A and P = 0.0005 for Luminal B subtype), while in normal-like breast cancer subtype, RKIP expression was not informative. RKIP expression was prognostic in ER+ and ER- subgroups. RKIP expression had no significant prognostic power within Basal-like, Claudine-low, Luminal B, or Her-2-enriched breast cancer subtypes. However, its expression pinpointed excellent from intermediate-poor Luminal A survivors, in both ER+ (P = 0.035) and ER- (P = 0.012) subgroups, especially in LN negative breast cancers. In conclusion, RKIP expression adds significant value to the molecular subclassification of breast cancer especially for the Luminal A subtype.
authors.affiliation: Department of Pathology, Faculty of Medicine, Kuwait University Health Sciences Centre, Safat, 13110, Kuwait.
authors.forename: Fahd
authors.initials: F
authors.lastname: Al-Mulla
authors.forename: Makia
authors.initials: M
authors.lastname: Marafie
authors.forename: Tuan
authors.initials: T
authors.lastname: Zea Tan
authors.forename: Jean
authors.initials: J
authors.lastname: Paul Thiery
mesh_terms: D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D049488:Phosphatidylethanolamine Binding Protein / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000302:isolation & purification* / Q000378:metabolism
chemical_list: D049488:Phosphatidylethanolamine Binding Protein; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human
keywords: AGGRESSIVE CANCER; BASAL; BREAST CANCER; CLAUDIN-LOW; DISEASE-FREE SURVIVAL; ERBB2; ERK; ESTROGEN RECEPTOR; LUMINAL A; PEBP1; PROGNOSIS; RKIP