The Identification of Gene Expression Profiles Associated with Granulomatous Mastitis

Abstract

Background: Granulomatous mastitis (GM) is a rare chronic inflammatory disease of the breast. The current therapeutic effects of the antibiotic therapy and surgical or immunomodulatory (steroid) treatment are normally poor due to the unclear etiology.

Method: This study aimed to identify the differentially expressed mRNAs in GM tissues using RNA sequencing and further explored the functions of differentially expressed mRNAs resulting in GM. Moreover, we revealed the relationship between GM and breast cancer by shared highly expressed genes in GM tissues and breast cancer tissues.

Results: A total of 12,115 mRNAs were analyzed in the whole expression profile, and 207 mRNAs (136 upregulated and 71 downregulated mRNAs) were differently expressed between the GM tissues and normal tissues. The enrichment analysis showed that the differentially expressed mRNAs were enriched in the biological processes and played a significant role in the immune system. Besides, the genes expressed significantly highly in breast cancer tissues are found to be enriched with GM genes, which may explain the similar clinical features between breast cancer and GM. We also found that the HSD11B1 gene which was differentially expressed in GM was used as drug target of prednisone, which is a common treatment for GM.

Conclusion: This study is the first to use sequencing technology to elucidate the genetic mechanisms of GM. The finding of this study may have potential value in GM diagnosis and also provides potential drug targets for GM treatment.

Keywords: Etiology; Expression profiles; Granulomatous mastitis; RNA sequencing.

Fig. 1

a Volcano plot of differentially expressed mRNAs between GM and control groups. Expression levels are represented in red and blue, where red shows higher expression and blue shows lower expression. b Hierarchical cluster heat map of expression levels of mRNAs between GM and control groups.

Fig. 2

Top 20 gene ontology (GO) terms ranked by n-fold enrichment and enrichment score are shown by GO analysis of the differentially expressed genes. Molecular function (MF), cellular component (CC), and biological process (BP) are represented by green, red, and blue, respectively.

Fig. 3

A network consisting of differentially expressed mRNAs. The colored mRNAs reflect the expressed mRNAs related to the immune system. Boxes A and B show two groups of immune system-related mRNAs.

Fig. 4

Gene ontology (GO) terms ranked by n-fold enrichment and enrichment score are shown by GO analysis of the GM genes expressed significantly highly in breast cancer tissues. Molecular function (MF), cellular component (CC), and biological process (BP) are represented by green, red, and blue, respectively.

Fig. 5

a–e The expression level of 5 RNAs, including MUCL1 (a), AP1M2 (b), S100A1 (c), MMP9 (d), and CYP27B1 (e).