Distinctive gene expression patterns in pregnancy-associated breast cancer

Abstract

Pregnancy-associated breast cancer (PABC) is diagnosed during pregnancy or within 1 year postpartum, but the unique aspects of its etiology and pathogenesis have not been fully elucidated. This study aimed to ascertain the molecular mechanisms of PABC to facilitate diagnosis and therapeutic development. The Limma package was used to characterize the differentially expressed genes in PABC as compared to non-pregnancy-associated breast cancer (NPABC) and normal breast tissue. A total of 871 dysregulated genes were identified in the PABC versus NPABC groups and 917 in the PABC versus normal groups, with notable differences in the expression of MAGE and CXCL family genes. The dysregulated genes between the PABC and normal groups were mainly associated with signal transduction and immune response, while Kyoto Encyclopedia of Genes and Genomes analysis revealed that the dysregulated genes were enriched in immune-related pathways, including the major histocompatibility complex (MHC) class II protein complex, the type I interferon signaling pathway, regulation of α-β T-cell proliferation, and the T-cell apoptotic process. Through protein-protein interaction network construction, CD44 and BRCA1 were identified as prominent hub genes with differential expression in PABC versus NPABC. Furthermore, a cluster with eleven hub genes was identified in PABC versus normal adjacent tissues, of which the expression of EGFR, IGF1, PTGS2, FGF1, CAV1, and PLCB1 were verified to be differentially expressed in an independent cohort of PABC patients. Notably, IGF1, PTGS2, and FGF1 were demonstrated to be significantly related to patient prognosis. Our study reveals a distinctive gene expression pattern in PABC and suggests that IGF1, PTGS2, and FGF1 might serve as biomarkers for diagnosis and prognosis of PABC.

Clinicopathologic features, treatment, and prognosis of pregnancy-associated breast cancer

“…( 21 )observed that among a cohort of 20 PABC patients, 35% of PABC patients tested carried pathogenic mutations in BRCA1 and CHEK2 genes. Some patients carrying germline mutations did not report a family history of cancer ( 21 ).Thus, highlighting the genomics of PABC and examining all biological pathways will further facilitate the identification of novel biomarkers defining women who are at high risk of developing PABC in the general population ( 18 , 22 ). BC-PP is also more unfavorable, as the rate of HER-2 positive and Ki-67≥20% was significantly higher than that of its controls (P=0.01, 0.018, respectively), although age, year of diagnosis, and TNM stage were well matched.…”

Breast Carcinogenesis during Pregnancy: Molecular Mechanisms, Maternal and Fetal Adverse Outcomes

“…Significant differences are also detected regarding gene expression patterns in breast tumors detected in patients with PABC and non-pregnancy-associated breast cancer [ 35 ]. PABC epithelial cells have additional copy numbers of DNA coding genes for morphogenesis, angiogenesis and metastases, as well as fewer copy numbers of DNA coding genes for tumor suppressors, cell adhesion, macromolecular complex assembly, and intra-cellular trafficking, changes that accumulatively lead to increased invasiveness and biological aggressiveness [ 25 , 27 ].…”