Abstract
We investigated the gene expression profiles of calcifications in breast cancer. Gene expression analysis of surgical specimen was performed using Affymetrix GeneChip® Human Gene 2.0 ST arrays in 168 breast cancer patients. The mammographic calcifications were reviewed by three radiologists and classified into three groups according to malignancy probability: breast cancers without suspicious calcifications; breast cancers with low-to-intermediate suspicious calcifications; and breast cancers with highly suspicious calcifications. To identify differentially expressed genes (DEGs) between these three groups, a one-way analysis of variance was performed with post hoc comparisons with Tukey’s honest significant difference test. To explore the biological significance of DEGs, we used DAVID for gene ontology analysis and BioLattice for clustering analysis. A total of 2551 genes showed differential expression among the three groups. ERBB2 genes are up-regulated in breast cancers with highly suspicious calcifications (fold change 2.474, p < 0.001). Gene ontology analysis revealed that the immune, defense and inflammatory responses were decreased in breast cancers with highly suspicious calcifications compared to breast cancers without suspicious calcifications (p from 10−23 to 10−8). The clustering analysis also demonstrated that the immune system is associated with mammographic calcifications (p < 0.001). Our study showed calcifications in breast cancers are associated with high levels of mRNA expression of ERBB2 and decreased immune system activity.
Highlights
Mammography is an established screening tool for breast cancer and calcifications are one of the most important findings for the detection of breast cancer[1, 2]
We searched for gene expression profiles of breast cancers with suspicious calcifications and compared those with gene expression profiles of breast cancers without suspicious calcifications
Breast cancers with highly suspicious calcifications are associated with high levels of mRNA expression of ERBB2 and decreased expression of COL11A1 and FNDC1
Summary
Mammography is an established screening tool for breast cancer and calcifications are one of the most important findings for the detection of breast cancer[1, 2]. The detection and characterization of calcifications are important in preoperative evaluations of lesion extent and surveillance after treatment in breast cancer patients[3, 4]. Previous studies have attempted to evaluate and interpret the relationship between mammographic calcifications and tumor histology or the expression of selected biological markers, such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), using immunohistochemistry and have shown that breast cancers with mammographic calcifications are more frequently associated with invasive cancer with extensive ductal carcinoma in situ (DCIS) or HER2-positive breast cancer[15,16,17,18,19,20]. The mainstay of radiogenomic studies often uses magnetic resonance imaging and showed association between several imaging features and genomic data. The purpose of this study was to investigate the gene expression profiles of calcifications in breast cancer
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