Distinctive gene expression patterns in pregnancy-associated breast cancer

Dan Wang; Huiyu Peng; Yuyao Hu; Xue Piao; Dianshuai Gao; Yan Sha

doi:10.3389/fgene.2022.850195

Distinctive gene expression patterns in pregnancy-associated breast cancer

Front Genet. 2022 Aug 10:13:850195. doi: 10.3389/fgene.2022.850195. eCollection 2022.

Authors

Dan Wang¹, Huiyu Peng², Yuyao Hu³, Xue Piao¹, Dianshuai Gao⁴, Yan Sha¹

Affiliations

¹ School of Medical Information and Engineering, Xuzhou Medical University, Xuzhou, China.
² The Key Laboratory of BioMedical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Suzhou, China.
³ School of Life Science, Xuzhou Medical University, Xuzhou, China.
⁴ Research Center for Neurobiology of Xuzhou Medical University, Xuzhou, China.

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.

Keywords: GEO; breast cancer; expression profiling; immune; pregnancy.