Abstract 758: Differential gene expression profiling of matched primary and metastatic triple negative breast cancer
Authors: Kaur Jaspreet 
Published: June 2022

Abstract
Background: Triple negative breast cancer (TNBC) is a molecularly complex and heterogeneous subtype of breast cancer with distinct biological features and clinical behavior. TNBC is associated with increased risk of metastasis and recurrence. To identify the underlying transcriptional changes and differentially expressed genes in metastatic progression of TNBC, we compared the transcriptomic profile of primary and matched metastatic tumors using massively parallel RNA sequencing.
Methods: We performed gene expression profiling using paraffin embedded formalin fixed tissues of 38 TNBC patients obtained from University Hospital Zurich, Switzerland and Stavanger University Hospital, Norway. Of these, 18 were primary TNBC tumors that did not metastasize; 20 patients metastasized to lymph nodes or to distant organs (16 paired primary and metastatic tumors). Absolute fold change of ≥ 2 and a p-value &lt;0.05 was used as the cutoff to identify significant differentially expressed genes (DEGs). Functional analysis was performed on DEGs. We also compared gene-expression profiles for hypoxia related- and EMT-related genes between our comparison groups. CIBERSORT analysis was used to estimate relative fractions of 22 immune cell types in each RNA-seq sample.
Results: We identified 2442 DEGs between primary TNBC tumors and corresponding metastatic lesions and 1561 DEGs between metastasis-free and metastatic primary tumors. Of the 2442 DEGs between primary and metastatic tumors, we found 579 genes to be upregulated and 1863 genes to be downregulated in primary tumors compared to matched metastatic tumors. A total of 530 genes were found to be upregulated and 1031 genes were downregulated in metastasis-free compared to metastatic primary TNBC tumors. Of the 27 gene hypoxia signature, only 1 gene (MPRS17) was significantly different between primary and corresponding metastatic tumors and 3 hypoxia-related genes (KCTD11, FOSL1 and SDC1) showed significant differences between primary tumors with and without metastasis. We found expression for 1 EMT related gene (TWIST1) to be different between primary and matched metastatic tumors whereas 4 EMT related genes (CDH2, VIM, SNAI1 and FOXC2) were found to be significantly different between primary tumors that metastasized compared to primary tumors that remained metastasis-free. The relative fractions of 3 immune cell types, T cells CD4 memory resting, M2 macrophages and M0 macrophage were similar between the primary tumor and their matched metastatic lesions.
Conclusions: Our results show that distinct patterns of gene expression exist between primary TNBCs and matched metastatic tumors. Further studies are warranted to explore whether these discrete expression profiles underlie or derive from disease status.
Citation Format: Jaspreet Kaur. Differential gene expression profiling of matched primary and metastatic triple negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 758.