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
School of Medicine, International Medical University, Kuala Lumpur, Malaysia.
School of Medicine, International Medical University, Kuala Lumpur, Malaysia.
Surg Oncol. 2021 Jun;37:101536. doi: 10.1016/j.suronc.2021.101536. Epub 2021 Mar 2.
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.
乳腺纤维腺瘤有两种表型变体。常见类型直径为5厘米或更小，还有另一种大的变体称为巨大纤维腺瘤，其直径大于5厘米。尽管体积大，但它并非恶性。我们研究的目的是确定这种大的变体在生物学途径和生物标志物方面是否与常见的纤维腺瘤不同。
从44个纤维腺瘤和36个巨大纤维腺瘤中提取mRNA，并进行转录组分析，以确定巨大纤维腺瘤与纤维腺瘤相比上调和下调的基因。
与乳腺纤维腺瘤相比，巨大纤维腺瘤中共有40个基因显著上调，18个基因显著下调。上调的前5个基因是FN1、IL3、CDC6、FGF8和BMP8A。下调的前5个基因是TNR、CDKN2A、COL5A1、THBS4和BMPR1B。发现差异表达基因（DEGs）与参与细胞生长（PI3K-AKT、细胞周期调节、WNT和RAS信号传导）和免疫反应（JAK-STAT信号传导）的5条主要经典途径相关。使用3种监督学习算法进行的进一步分析确定了一个8基因特征（FN1、CDC6、IL23A、CCNA1、MCM4、FLT1、FGF22和COL5A1），该特征能够以高预测准确性区分巨大纤维腺瘤和纤维腺瘤。
我们的研究结果表明，巨大纤维腺瘤在生物学上与乳腺纤维腺瘤不同，参与细胞生长和免疫反应调节的基因过表达。
