Uncovering Common Threads: Leveraging the Equivalent Expression Index to Reveal Shared Tumor–Microenvironment Signals in Breast Cancer Brain Metastases

Maxine Umeh Garcia, PhD, Instructor, Department of Neurosurgery

Friday, May 16, 2025
11:00am - 12:00pm  
James H. Clark Center, Room S360, 3rd floor next to the Coffee Shop
Zoom link

Abstract

Brain metastases (BrMets), common for advanced-stage breast cancer patients, are associated with poor median survival and accompanied by severe neurologic decline. Halting the progression of breast cancer brain metastases (BCBMs) may require modulation of the tumor microenvironment (TME), yet little is known about the impact of the primary breast TME on brain tropism, or how, once there, metastatic breast cancer cells coexist with brain-resident cells (e.g., neurons and glia). Traditionally, studies in this space have focused on differential expression analysis, overlooking potential insights gained from investigating genes with equivalent expression between groups. This is particularly crucial in distant metastasis, where tumor cells may co-opt the transcriptional programs of the host organ (e.g., brain) to facilitate successful seeding and outgrowth. Prior to our work, no computational framework existed to determine biologically-relevant equivalent gene expression. To resolve molecular mechanisms of BCBM enabled by metastatic cancer cells and/or resident brain cells, we leveraged Nanostring GeoMx to perform spatially-resolved transcriptomic profiling on 235 patient-derived tissue cores from BCBM (including adjacent normal brain), primary invasive breast cancers, and normal (non-cancer) brain; analyzing 18,677 RNAs in 450 areas of interest (AOIs). We introduce the “Equivalent Expression Index” a highly specific and accurate algorithm that identifies statistically significant "Equivalently-Expressed Genes". This method facilitated the identification of molecular remodeling and mimicry genes within tissue-specific TMEs. By integrating differential expression analysis with the Equivalent Expression Index, we discovered multiple novel gene signatures associated with BCBM and primary tumor brain-metastatic potential. We demonstrate that the Equivalent Expression Index is a powerful tool to uncover shared gene expression programs representing the adaptation of metastatic cells and brain-resident cells to the BCBM microenvironment.

Biography

Dr. Umeh Garcia transferred from a community college to UC Merced, where she earned a B.S. in Developmental Biology with a minor in Psychology and gained her first research experience in nervous system development. She continued at UC Merced to pursue a master’s in Quantitative and Systems Biology before earning a Ph.D. in Biochemistry, Molecular, Cellular, and Developmental Biology at UC Davis (with a designated emphasis in Translational Research), where her dissertation focused on triple-negative breast cancer. Now an Instructor in the Department of Neurosurgery at Stanford, she leads systems-level approaches to investigate the tumor microenvironment (TME) of breast cancer brain metastases. By integrating experimental and bioinformatic methods, her work has revealed novel gene signatures linked to the metastatic potential of primary breast cancers to the brain. She has also developed a novel technique to profile human cerebrospinal fluid (CSF) in patients with brain metastases for biomarker identification. Committed to diversity in biomedical science, she actively mentors both women and underrepresented minority students while working to enhance inclusion in academic research.