Dastsooz Hassan, Anselmi Francesca, Lauria Andrea, Cicconetti Chiara, Proserpio Valentina, Mohammadisoleimani Elham, Firoozi Zahra, Mansoori Yaser, Haghi-Aminjan Hamed, Caizzi Livia, Oliviero Salvatore
Department of Life Sciences and Systems Biology, University of Turin, Turin, Italy.
IIGM-Italian Institute for Genomic Medicine, IRCCS, Candiolo, TO, Italy.
Front Cell Dev Biol. 2024 May 24;12:1295403. doi: 10.3389/fcell.2024.1295403. eCollection 2024.
Patients with breast cancer show altered expression of genes within the pectoralis major skeletal muscle cells of the breast. Through analyses of The Cancer Genome Atlas (TCGA)-breast cancer (BRCA), we identified three previously uncharacterized putative novel tumor suppressor genes expressed in normal muscle cells, whose expression was downregulated in breast tumors. We found that NEDD4 binding protein 2-like 1 (), pleckstrin homology domain-containing family A member 4 (), and brain-enriched guanylate kinase-associated protein () that are normally highly expressed in breast myoepithelial cells and smooth muscle cells were significantly downregulated in breast tumor tissues of a cohort of 50 patients with this cancer. Our data revealed that the low expression of in patients with menopause below 50 years correlated with a higher risk of breast cancer. Moreover, we identified and as potential biomarkers of HER2-positive breast cancer. Furthermore, low expression in breast cancer patients with blood fat, heart problems, and diabetes correlated with a higher risk of this cancer. In addition, protein and RNA expression analysis of TCGA-BRCA revealed as a promising diagnostic protein biomarker in breast cancer. In addition, the data of scRNA-seq showed high expression of these genes in several cell types of normal breast tissue, including breast myoepithelial cells and smooth muscle cells. Thus, our results suggest their possible tumor-suppressive function in breast cancer and muscle development.
乳腺癌患者的乳腺胸大肌骨骼肌细胞内基因表达发生改变。通过对癌症基因组图谱(TCGA)-乳腺癌(BRCA)数据的分析,我们鉴定出三个在正常肌肉细胞中表达但此前未被表征的假定新型肿瘤抑制基因,它们在乳腺肿瘤中的表达下调。我们发现,在乳腺肌上皮细胞和平滑肌细胞中通常高表达的NEDD4结合蛋白2样1()、含pleckstrin同源结构域的A家族成员4()和脑富集鸟苷酸激酶相关蛋白(),在一组50例该癌症患者的乳腺肿瘤组织中显著下调。我们的数据显示,50岁以下绝经患者中该基因的低表达与乳腺癌风险较高相关。此外,我们鉴定出该基因和另一基因作为HER2阳性乳腺癌的潜在生物标志物。此外,在患有高血脂、心脏问题和糖尿病的乳腺癌患者中,该基因的低表达与患癌风险较高相关。此外,对TCGA-BRCA的蛋白质和RNA表达分析显示,该基因是乳腺癌中一种有前景的诊断蛋白质生物标志物。此外,单细胞RNA测序(scRNA-seq)的数据显示,这些基因在正常乳腺组织的几种细胞类型中高表达,包括乳腺肌上皮细胞和平滑肌细胞。因此,我们的结果提示它们在乳腺癌和肌肉发育中可能具有肿瘤抑制功能。