A novel group of genes that cause endocrine resistance in breast cancer identified by dynamic gene expression analysis
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Arvand Asghari1,*, Katherine Wall2,*, Michael Gill2, Natascha Del Vecchio3, Farnaz Allahbakhsh1, Jacky Wu1, Nan Deng4, W. Jim Zheng5, Hulin Wu2, Michihisa Umetani1,6 and Vahed Maroufy2
1 Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, USA
2 Department of Biostatistics and Data Science, School of Public Health, UTHealth, Houston, TX 77030, USA
3 Chicago Center for HIV Elimination, University of Chicago, Chicago, IL 60637, USA
4 Clinical Cancer Prevention Department, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
5 School of Biomedical Informatics, UTHealth, Houston, TX 77030, USA
6 Health Research Institute, University of Houston, Houston, TX 77204, USA
* These authors contributed equally to this work
Keywords: breast cancer; triple negative breast cancer; gene expression profiling; endocrine resistance; gene clustering
Received: February 15, 2022 Accepted: March 25, 2022 Published: April 06, 2022
Breast cancer (BC) is the most common type of cancer diagnosed in women. Among female cancer deaths, BC is the second leading cause of death worldwide. For estrogen receptor-positive (ER-positive) breast cancers, endocrine therapy is an effective therapeutic approach. However, in many cases, an ER-positive tumor becomes unresponsive to endocrine therapy, and tumor regrowth occurs after treatment. While some genetic mutations contribute to resistance in some patients, the underlying causes of resistance to endocrine therapy are mostly undetermined. In this study, we utilized a recently developed statistical approach to investigate the dynamic behavior of gene expression during the development of endocrine resistance and identified a novel group of genes whose time course expression significantly change during cell modelling of endocrine resistant BC development. Expression of a subset of these genes was also differentially expressed in microarray analysis of endocrine-resistant and endocrine-sensitive tumor samples. Surprisingly, a subset of those genes was also differentially genes expressed in triple-negative breast cancer (TNBC) as compared with ER-positive BC. The findings suggest shared genetic mechanisms may underlie the development of endocrine resistant BC and TNBC. Our findings identify 34 novel genes for further study as potential therapeutic targets for treatment of endocrine-resistant BC and TNBC.
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