Abstract P3-01-04: Differential Gene Expression Analysis among Post-Menopausal Caucasian Invasive Breast Cancer, Benign and Normal Subjects
Authors: Saini J , Li X , Kvecher L , Larson C , Croft D , Yang Y-C , Hooke JA , Shriver CD , Mural RJ , Hu H. 
Published: April 2011

Background: Breast Cancer (BC) is the second leading cause of cancer death among women in United States. There have been studies aiming to develop a blood-based BC detection assay, but most were focused on comparing blood samples between BC and normal subjects. Including benign disease patients in the study is critical in developing a BC detection assay. In addition, BC is a heterogeneous disease with distinct characteristics being associated with ethnicity and menopausal status. Thus we designed a study to analyze gene expression, in peripheral blood samples from invasive BC, benign disease and normal subjects, stratified by menopausal status and ethnicity. Here we report the results from Caucasian postmenopausal women.

Method: Subjects were selected from the Clinical Breast Care Project (CBCP). Microarray data using Affymetrix GeneChip Human Genome U133 plus 2.0 arrays, of peripheral blood samples from pathologically confirmed invasive BC (n= 17) and benign patients (n= 17) were compared to those from normal subjects (n=17). All subjects were postmenopausal Caucasian women, matched for age. Using GenespringGX 11.0 software, the data were normalized, and QC on hybridization and internal controls were performed before filtering out probesets with the lowest 20% signal intensity in each array. Asymptotic t-test with FDR correction was used and significant pathways were obtained.

Results: Comparison of gene expression in invasive BC patients (mean±SD = 63.7±7.0 years old) vs. normal subjects (mean±SD = 63.2±7.4 years) identified 1102 significantly different genes, satisfying the thresholds of corrected p &lt; 0.05 and Fold Change (FC) &gt; 1.5. Of them, 1003 genes were up regulated and 99 genes were down regulated in BC patients. Comparison of gene expression in benign disease women (mean±SD = 61.4±10.4 years) vs. normal women showed 1320 significantly different genes (corrected p &lt; 0.05, FC &gt; 1.5), with 1121 genes being up regulated and 199 genes being down regulated in benign patients. Of the top 10 genes with highest FC values, 6 genes (MBNL1, FAR1, MDM4, ITGA4, RAB8B, and EXOC5) were common in both analyses and were up regulated. NOTCH pathway was up regulated in both benign (p=0.038) and invasive (p=0.042) groups. Similarly, IL-7 pathway was up regulated in both benign (p=0.047) and invasive (p=0.030) patients. TCR pathway (p=7.36E-04) was up regulated in benign group only. The benign vs. invasive BC subjects did not show significant differential gene expression.

Discussion: Our results provide a list of differentially expressed genes that are mostly up regulated in invasive and benign patients vs. normal subjects. NOTCH pathway is involved in cell-cell communication and angiogenesis. IL7 pathways play an important role in immune system response, cell proliferation and cell survival signaling. TCR pathway is highly significant only in benign patients and stimulation of TCR pathway induces a signaling cascade that ultimately results in activation of induced cell death. This activation could be early body response to prevent cancer development in benign subjects. When more microarray analyses are completed for this study, we hope to obtain a better understanding of the possibility of developing a blood-based BC detection assay.

Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P3-01-04.