10168- GEN-11 GENETIC ANALYSIS OF PRIMARY BREAST CANCER TUMORS AND BRAIN METASTASIS TUMORS WITH RNA-SEQ

Abstract BACKGROUND Breast cancer is the most common malignancy in women; brain metastasis is a marked cause of mortality. Recent genomic studies have identified distinct genetic profiles in brain metastases, suggesting unique mechanisms underlying treatment resistance. This study aimed to compare gene expression in primary breast tumors and the corresponding brain metastases to identify potential biomarkers and therapeutic targets. METHODS Eight paired samples of primary breast tumors and brain metastases from patients who developed brain metastases after radical mastectomy were analyzed. RNA sequencing was used to comprehensively assess gene expression differences between the two tumor types. RESULTS RNA sequencing revealed 391 downregulated and 474 upregulated genes in brain metastases compared to primary tumors. Gene set enrichment analysis revealed that epithelial-mesenchymal transition (EMT)-associated genes (SPP, GREM1, and MMP3) were upregulated in primary breast tumors. Conversely, reactive oxygen species (ROS)-related genes (GPX4 and PRDX family members) were upregulated in brain metastases. CONCLUSION High expression of EMT-related genes in primary tumors indicates that these tumors prepare for metastasis by inducing EMT during radical resection, enabling tumors to invade the surrounding tissues and metastasize to distant organs. Additionally, ROS-related genes are highly expressed in metastatic brain tumors, suggesting that these genes contribute to tumor enhancement at the metastatic site. These findings could aid in development of biomarkers for predicting brain metastasis and for identifying novel therapeutic targets. In future, we aim to analyze tumor localization and functions of these gene products.