Open AccessAbstract 2698: Spatial gene expression profiling in breast cancer
Author(s) -
Melanie Spears,
Vida Talebian,
Linda M. Liao,
Megan Hopkins,
Drashti Jain,
Mary Anne Quintayo,
Jane Bayani,
Alison Cheung,
Martin D. Yaffe,
John M.S. Bartlett
Publication year - 2021
Publication title -
cancer research
Language(s) - English
Resource type - Conference proceedings
SCImago Journal Rank - 1.055
H-Index - 84
eISSN - 1538-7445
pISSN - 0008-5472
DOI - 10.1158/1538-7445.am2021-2698
Subject(s) - breast cancer , lumpectomy , immune system , transcriptome , cancer research , cancer , medicine , gene expression profiling , pathology , biology , immunology , mastectomy , gene , gene expression , biochemistry
Over the last decade breast cancer survival has improved, largely due to the therapies offered to patients with the disease. However, despite the advances in diagnosis and treatment of breast cancer, it is still remains the second leading cause of death from cancer in women. Breast cancer is a heterogeneous disease, this in part, explains why the majority of current therapeutic approaches for cancer work best when multiple agents are combined. The interaction between immune and tumor cells is critical in the development and progression of breast cancer. Here we present in situ transcriptomic profiling, using the NanoString Digital Spatial Profiler (DSP) cancer transcriptomic atlas (CTA) assay, of a cohort of breast cancer lumpectomies to reveal the extent of heterogeneity in pathologically defined unifocal and multifocal cancers. In this study, lumpectomies were processed as whole mounts with serial blocks reviewed. Tissue cores were taken from at least three different regions through the lumpectomy for tissue microarray (TMA) construction, focusing on morphologic/histological differences in addition to the spatial orientation of the sampled region within the lumpectomy. In situ quantification of 1800 tumor and immune genes across 60 patients revealed heterogeneity of tumor and immune genes in most patients. Expression of genes such as HER2, ER and AKT were enriched in the tumor compartment. Whereas, genes such as COLA1, CD68 and CD3 were enriched in the immune compartment. Using a SpatialDecon algorithm for mixed cell deconvolution on the immune areas heterogeneity of the tumor infiltrate at a cell type levels was observed. Fibroblasts and macrophages were prevalent in all samples while immune dense areas also contained B-cells and T-cells. While there are a number of clinically validated transcriptional assays available for breast cancer, we have demonstrated that the immune microenvironment needs to be considered to develop rational stratification of patients to currently available targeted therapies. Citation Format: Melanie Spears, Vida Talebian, Linda Liao, Megan Hopkins, Drashti Jain, Mary Anne Quintayo, Jane Bayani, Alison Cheung, Martin Yaffe, John M. Bartlett. Spatial gene expression profiling in breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2698.