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Optimization of a Multiplex RNA-based Expression Assay Using Breast Cancer Archival Material
Published on: August 1, 2018
Clinical Significance of Tumor Invasion Gene Profiling in Early-Stage Hormone Receptor-Positive Breast Cancer: A
Shayan Forghani1, Hamid Rezvani2, Arman Forghani1
1Cancer Research Center Shahid Beheshti University of Medical Sciences Tehran Iran.
Background And Aims:
Advanced breast cancer is a leading cause of cancer-associated death in women. It is critical to find biomarkers to identify patients who are more prone to progress to advanced disease and would be better served with more aggressive treatments. Hormone receptor-positive breast cancers make up about 70% of all breast cancers. The analysis of gene amplification and expression has been utilized to classify breast tumors into medically useful risk groups. In the present study, we selected five genes (MMP11, CTSV, CD68, SCUBE2, and MYBL2) that are important in tumor invasion and metastasis to identify a pattern associated with well-established pathology markers indicative of poor prognosis in early-stage hormone receptor-positive breast cancers.
Methods:
Two hundred and thirty-nine early-stage hormone receptor-positive breast cancer patients were analyzed. Patients were required to have FFPE (formalin-fixed paraffin-embedded) samples from the primary tumor. Expression of the selected genes was determined using TaqMan expression assays. MYBL2 amplification was examined using fluorescent in situ hybridization (FISH).
Results:
Expression of CTSV was significantly associated with increasing tumor size (p = 0.001) and lymph node involvement (p = 0.016). In multivariate analysis, CTSV expression remained significantly associated with lymph node involvement (p = 0.049). Expression of MYBL2 was associated with higher tumor grade (p = 0.001). We identified MYBL2 amplification in one sample. Expression of SCUBE2 was inversely associated with tumor grade (p = 0.04). Receiver-operator characteristic (ROC) analysis was used to predict lymph node involvement using clinicopathologic features (age at diagnosis, tumor size, and histologic grade), and the five gene expression markers, which resulted in AUC = 0.83.
Conclusion:
We found a significant association between CTSV, MYBL2, and SCUBE2 expression and pathological variables of poor prognosis. Our study reveals that analysis of the expression of these genes may help identify early-stage hormone receptor-positive breast tumors that are more likely to metastasize and need more intense treatment modalities.