1st International and 10th National Iranian Conference on Bioinformatics
Home Accepted Papers
Agonist/ antagonist compounds' mechanism of action on estrogen receptor-positive breast cancer: a system-level investigation assisted by meta-analysis
Paper ID : 1320-ICB10
Authors:
Zeynab Piryaei *1, Zahra Salehi2, mohammadreza Tahsili3, esmaeil ebrahimie4, Mansour Ebrahimi3, Kaveh Kavousi5
1دانشکاه تهران
2دانشگاه علوم پزشکی تهران
3دانشگاه قم
4دانشگاه شیراز
5University of Tehran
Abstract:
The largest group of breast cancer patients are estrogen receptor-positive (ER+) [1, 2]. There is a vast amount of studies focused on breast cancer. That vastness provides the requisites for the integration and meta-analysis of the related studies. Meta-analysis could lead to more accurate results than single investigations.
In the present work, a specific layout for meta-analysis of multiple RNA-seq datasets is proposed in order to obtain a final accurate, least error-prone methodology. Meta-analysis was separately performed on two estrogen-treated MCF7 and T47D versus untreated cell lines to obtain meta-differentially expressed genes. Also, only shared significant genes between MCF7 and T47D cell lines were enriched to obtain more stringent results. The ER+ patients respond to both ER agonist (E2) and ER antagonists (Tamoxifen, Fulvestrant, and Brilanestrant). Hence, we compared the meta-analysis results with genes obtained from ER antagonists to understand the function of ER and its affected genes. Genes involved in human mitochondria and several keratin family members' genes were up-regulated in the meta-analysis. Still, they showed no alteration neither in individual datasets treated with E2 and ER antagonists. Our findings indicated that Tamoxifen does not block specific genes directly affected by ER and has no effect on their expression. Moreover, to the best of the authors' knowledge, pathways were identified that were not previously reported in BC. Meta-analysis of RNA-seq data with correct methodology could identify new genes and pathways that are essential in breast cancer. If there are suitable datasets, it is recommended that the methodology be used for other diseases to obtain more accurate results.
Keywords:
Breast cancer; Estrogen receptor positive; ER agonist/antagonist; RNA-sequencing; Meta-analysis; MCF7/T47D cell lines
Status : Paper Accepted (Poster Presentation)