Ann Ramsdell, PhD, University of South Carolina School of Medicine
PROJECT TITLE: Left-right analysis of mammary tumors and their microenvironment by RNA-seq
Survival rates for patients with cancer of the breast or other paired organs differ according to the side of the body on which the tumor forms. This project uses a triple negative breast cancer mouse model to probe for left versus right differences in gene expression that may promote differences in tumor progression and metastasis. In the long term, results from this study will increase understanding of how tumor malignancy is regulated and are anticipated to lead to identification of molecular targets that can be harnessed into biologically based prevention and treatment strategies for triple negative breast cancer.
This pilot project investigates a clinically significant but poorly understood aspect of breast cancer, which is that greater metastatic activity and poorer patient survival are associated with right (versus left) breast tumors. Using a triple negative breast cancer mouse model, our experimentally generated tumors recapitulate the greater right side tumor malignancy that is reported for breast cancer patients. The objectives of this study are to use RNA-Seq to determine if there are differences in gene expression in left versus right mouse mammary tumors and tissues. Results are anticipated to determine whether situs-dependent transcriptional regulation occurs in paired-organ malignancies, and if so, to identify pathways that represent putative biomarkers and therapeutic targets for triple negative breast cancer, an aggressive subtype for which biologically targeted therapies do not yet exist.
SC INBRE Bioinformatics Pilot Project Program funds supported the genomic analysis that led to discovery of differences in immune system response to left versus right mouse mammary tumors.
Bioinformatic analysis of RNA-seq data indicates significantly elevated adaptive immune response in left side triple negative mouse mammary tumor signatures. In addition to identification of immunological pathways that represent putative biomarkers and drug targets, these results also implicate laterality as previously unappreciated factor that may affect immunotherapeutic efficacy, including preclinical development and clinical trial evaluation of immune cell checkpoint inhibitors and breast cancer vaccines.
March 9, 2018