Effects of neoadjuvant therapies on genetic regulation of targeted pathways in ER+ primary ductal breast carcinoma: A meta-analysis of microarray datasets期刊界 All Journals 搜尽天下杂志传播学术成果专业期刊搜索期刊信息化学术搜索

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Effects of neoadjuvant therapies on genetic regulation of targeted pathways in ER+ primary ductal breast carcinoma: A meta-analysis of microarray datasets

Institution:	1. Department of Biotechnology, College of Science, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia;2. Department of Clinical Pharmacy, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia;3. Pharmaceutical Care Division, King Faisal Specialist Hospital and Research Center, P.O. Box 3354, MBC#11, Riyadh 11211, Saudi Arabia;4. International Medical Center Hospital, P.O. Box 953, Jeddah 21423, Saudi Arabia;5. Department of Surgery, College of Medicine, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia

Abstract:	Breast cancer arises as a result of multiple interactions between environmental and genetic factors. Conventionally, breast cancer is treated based on histopathological and clinical features. DNA technologies like the human genome microarray are now partially integrated into clinical practice and are used for developing new “personalized medicines” and “pharmacogenetics” for improving the efficiency and safety of cancer medications. We investigated the effects of four established therapies—for ER+ ductal breast cancer—on the differential gene expression. The therapies included single agent tamoxifen, two-agent docetaxel and capecitabine, or combined three-agents CAF (cyclophosphamide, doxorubicin, and fluorouracil) and CMF (cyclophosphamide, methotrexate, and fluorouracil). Genevestigator 8.1.0 was used to compare five datasets from patients with infiltrating ductal carcinoma, untreated or treated with selected drugs, to those from the healthy control. We identified 74 differentially expressed genes involved in three pathways, i.e., apoptosis (extrinsic and intrinsic), oxidative signaling, and PI3K/Akt signaling. The treatments affected the expression of apoptotic genes (TNFRSF10B TRAIL], FAS, CASP3/6/7/8, PMAIP1 NOXA], BNIP3L, BNIP3, BCL2A1, and BCL2), the oxidative stress-related genes (NOX4, XDH, MAOA, GSR, GPX3, and SOD3), and the PI3K/Akt pathway gene (ERBB2 HER2]). Breast cancer treatments are complex with varying drug responses and efficacy among patients. This necessitates identifying novel biomarkers for predicting the drug response, using available data and new technologies. GSR, NOX4, CASP3, and ERBB2 are potential biomarkers for predicting the treatment response in primary ER+ ductal breast carcinoma.

Keywords:	Chemotherapy ER+ ductal carcinoma GSR NOX4 CASP3 BC"} {"#name":"keyword" "$":{"id":"k0040"} "$$":[{"#name":"text" "_":"breast cancer ER"} {"#name":"keyword" "$":{"id":"k0050"} "$$":[{"#name":"text" "_":"estrogen receptor PR"} {"#name":"keyword" "$":{"id":"k0060"} "$$":[{"#name":"text" "_":"progesterone receptor HER2"} {"#name":"keyword" "$":{"id":"k0070"} "$$":[{"#name":"text" "_":"human epidermal growth factor 2 ROS"} {"#name":"keyword" "$":{"id":"k0080"} "$$":[{"#name":"text" "_":"reactive oxygen species OH●"} {"#name":"keyword" "$":{"id":"k0090"} "$$":[{"#name":"text" "_":"hydroxyl radical hydrogen peroxide Bcl2"} {"#name":"keyword" "$":{"id":"k0110"} "$$":[{"#name":"text" "_":"B-cell lymphoma 2 PI3K/Akt"} {"#name":"keyword" "$":{"id":"k0120"} "$$":[{"#name":"text" "_":"phosphatidylinositol 3-kinase/protein kinase B Bax"} {"#name":"keyword" "$":{"id":"k0130"} "$$":[{"#name":"text" "_":"Bcl-2-associated X FU"} {"#name":"keyword" "$":{"id":"k0140"} "$$":[{"#name":"text" "_":"fluorouracil TS"} {"#name":"keyword" "$":{"id":"k0150"} "$$":[{"#name":"text" "_":"thymidylate synthase DC"} {"#name":"keyword" "$":{"id":"k0160"} "$$":[{"#name":"text" "_":"docetaxel and capecitabine TMX"} {"#name":"keyword" "$":{"id":"k0170"} "$$":[{"#name":"text" "_":"tamoxifen TGF-α/β"} {"#name":"keyword" "$":{"id":"k0180"} "$$":[{"#name":"text" "_":"transforming growth factor alpha/beta IGF-1"} {"#name":"keyword" "$":{"id":"k0190"} "$$":[{"#name":"text" "_":"insulin-like growth factor-1 PM"} {"#name":"keyword" "$":{"id":"k0200"} "$$":[{"#name":"text" "_":"personalized medicine CAF"} {"#name":"keyword" "$":{"id":"k0210"} "$$":[{"#name":"text" "_":"cyclophosphamide doxorubicin and fluorouracil CMF"} {"#name":"keyword" "$":{"id":"k0220"} "$$":[{"#name":"text" "_":"cyclophosphamide methotrexate and fluorouracil PRISMA"} {"#name":"keyword" "$":{"id":"k0230"} "$$":[{"#name":"text" "_":"Preferred Reporting Items for Systematic Reviews and Meta-Analyses FC"} {"#name":"keyword" "$":{"id":"k0240"} "$$":[{"#name":"text" "_":"fold-change
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