Gene expression profiling of giant fibroadenomas of the breast

• Published in: Surgical oncology 2021-06, Vol.37, p.101536, Article 101536
• Main Authors: Yin Lee, June Pui, Thomas, Annamarie Jacob, Lum, Siew Kheong, Shamsudin, Noor Hasni, Hii, Ling-Wei, Mai, Chun-Wai, Wong, Shew-Fung, Leong, Chee-Onn
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Adolescent; Adult; AKT protein; Algorithms; Biomarkers; Breast; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Breastfeeding & lactation; Breasts; Cell cycle; Cell Cycle Proteins - physiology; Cell division; Clinical trials; Collagen Type V; Cytokines; DNA methylation; Female; Fibroadenoma; Fibroadenoma - genetics; Fibroadenoma - pathology; Fibroblast growth factor 8; Fibroblast Growth Factors; Fibroblasts; Fibronectins; Gene expression; Gene Expression Profiling; Gene profiling; Gene regulation; Genes; Genomes; Giant fibroadenoma; Growth factors; Humans; Immune response; Immune system; Interleukin 3; Interleukin-23 Subunit p19; Kinases; Learning algorithms; Machine learning; Middle Aged; Mutation; Patients; Predictive Value of Tests; Principal components analysis; Proteins; Signal transduction; Signal Transduction - physiology; Signaling; Software; Statistical analysis; Tumors; Vascular Endothelial Growth Factor Receptor-1; Wnt protein; Young Adult
• ISSN: 0960-7404; 1879-3320
• DOI: 10.1016/j.suronc.2021.101536

Fibroadenomas of the breast present as two phenotypic variants. The usual variety is 5 cm or less in diameter and there is another large variant called giant fibroadenoma which is greater than 5 cm in diameter. Despite of its large size, it is not malignant. The aim of our study is to determine whether this large variant is different from the usual fibroadenoma in terms of its biological pathways and biomarkers. mRNA was extracted from 44 fibroadenomas and 36 giant fibroadenomas, and transcriptomic profiling was performed to identify up- and down-regulated genes in the giant fibroadenomas as compared to the fibroadenomas. A total of 40 genes were significantly up-regulated and 18 genes were significantly down-regulated in the giant fibroadenomas as compared to the fibroadenomas of the breast. The top 5 up-regulated genes were FN1, IL3, CDC6, FGF8 and BMP8A. The top 5 down-regulated genes were TNR, CDKN2A, COL5A1, THBS4 and BMPR1B. The differentially expressed genes (DEGs) were found to be associated with 5 major canonical pathways involved in cell growth (PI3K-AKT, cell cycle regulation, WNT, and RAS signalling) and immune response (JAK-STAT signalling). Further analyses using 3 supervised learning algorithms identified an 8-gene signature (FN1, CDC6, IL23A, CCNA1, MCM4, FLT1, FGF22 and COL5A1) that could distinguish giant fibroadenomas from fibroadenomas with high predictive accuracy. Our findings demonstrated that the giant fibroadenomas are biologically distinct to fibroadenomas of the breast with overexpression of genes involved in the regulation of cell growth and immune response. •A total 40 genes were significantly up-regulated and 18 genes were down-regulated in the giant fibroadenomas (GFAs) vs fibroadenomas of the breast.•The differentially regulated genes were associated cell cycle regulation, PI3K-AKT, WNT, JAK-STAT and RAS signalling.•Up-regulation of FN1, CDC6, IL23A, CCNA1, MCM4, FLT1 and FGF22, and down-regulation of COL5A1 are significantly associated with GFAs.•The 8-gene signature could distinguish GFAs from fibroadenomas with high predictive accuracy.