Distinct gene expression profiles between primary breast cancers and brain metastases from pair-matched samples

• Published in: Scientific reports Vol. 9; no. 1; pp. 13343 - 8
• Main Authors: Iwamoto, Takayuki, Niikura, Naoki, Ogiya, Rin, Yasojima, Hiroyuki, Watanabe, Ken-ichi, Kanbayashi, Chizuko, Tsuneizumi, Michiko, Matsui, Akira, Fujisawa, Tomomi, Iwasa, Tsutomu, Shien, Tadahiko, Saji, Shigehira, Masuda, Norikazu, Iwata, Hiroji
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.09.2019; Nature Publishing Group
• Subjects: 45/61; 631/114/2407; 631/67/1347; Adult; Aged; Biomarkers, Tumor - genetics; Blood-Brain Barrier - physiology; Brain cancer; Brain Neoplasms - genetics; Brain Neoplasms - secondary; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; DNA (Cytosine-5-)-Methyltransferases - biosynthesis; DNA (Cytosine-5-)-Methyltransferases - genetics; Epithelial-Mesenchymal Transition - genetics; Female; Gene expression; Gene Expression Regulation, Neoplastic - genetics; Humanities and Social Sciences; Humans; Mesenchyme; Metastases; Metastasis; Middle Aged; multidisciplinary; Oncology; Platinum; Science; Science (multidisciplinary); Therapeutic applications; Toxicity; Transcriptome - genetics; Vascular Endothelial Growth Factor A - biosynthesis; Vascular Endothelial Growth Factor A - genetics
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-019-50099-y

Our objectives were to determine whether clinic-pathological markers and immune-related gene signatures in breast cancer exhibit any change upon brain metastasis and whether previously reported genes significantly associated with brain metastases and the epithelial-mesenchymal transition (EMT) were reproducible and consistent in our dataset. Sixteen pair-matched samples from primary breast cancers and brain metastases diagnosed were collected from the Japan Clinical Oncology Group Breast Cancer Study Group. Gene expression profiles for immune-, brain metastases-, and EMT-related genes were compared between primary breast cancers and brain metastases. Potential therapeutic target genes of 41 FDA-approved or under-investigation agents for brain metastases were explored. Immune-related signatures exhibited significantly lower gene expression in brain metastases than in primary breast cancers. No significant differences were detected for the majority of genes associated with brain metastases and EMT in the two groups. Among 41 therapeutic target candidates, VEGFA and DNMT3A demonstrated significantly higher gene expression in brain metastases. We found that distinct patterns of gene expression exist between primary breast cancers and brain metastases. Further studies are needed to explore whether these distinct expression profiles derive from or underlie disease status and compare these features between metastases to the brain and other sites.