FOXA1 expression in Iraqi women with ER+ breast cancer
DOI:
https://doi.org/10.47419/bjbabs.v2i02.43Keywords:
breast cancer, ER, FOXA1, immunohistochemistry, RT-qPCRAbstract
Background: Breast cancer (BC) is a heterogeneous disease that can be classified into many subtypes according to histopathological and molecular characteristics. Forkhead box protein A1 (FOXA1) is a transcriptional pioneer factor that opens chromatin allowing estrogen receptor (α-ER) access to its genomic targets. FOXA1 expression is related to luminal BC with a good prognosis.
Objectives: The present study is sought to determine the FOXA1 expression in Iraqi women with ER+ BC.
Methods: Forty-eight fresh malignant breast tissues were analyzed by immunohistochemistry assay to choose ER+ samples, and then by RT-qPCR to evaluate FOXA1 gene expression.
Results: The ER-positive samples were (72.91%) of the total samples, and the molecular subtype of luminal A was the most common with a percentage of 56.25%. It was also noted that the high expression of the FOXA1 gene is highly significant (p<0.05) in Iraqi women with BC when compared with healthy controls.
Conclusions: Highly significant FOXA1 expression was found in Iraqi women with BC makes it eligible to be a good predictor or a biomarker for BC.
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Alwan, N.A.S.; Tawfeeq, F. and Mallah. N.A.G.(2019). Demographic and clinical profiles of female patients diagnosed with breast cancer in Iraq. J Contemp Med Sci. 5 ( 1) 14–19. DOI: https://doi.org/10.22317/jcms.v5i1.544
Anita Mangia et al. “Should Tumor Infiltrating Lymphocytes, Androgen Receptor, and FOXA1 Expression Predict the Clinical Outcome in Triple Negative Breast Cancer Patients?” Cancers (Basel) 11(9) (2019), pp. 1393–1393. DOI: 10.3390/cancers11091393. DOI: https://doi.org/10.3390/cancers11091393
Antoni Hurtado et al. “FOXA1 is a key determinant of estrogen receptor function and endocrine response”. Nat Genet 43(1) (2011), pp. 27–33. DOI: 10.1038/ng.730. DOI: https://doi.org/10.1038/ng.730
Azizun-Nisa et al. “Comparison of ER, PR and HER-2/neu (C-erb B 2) reactivity pattern with histologic grade, tumor size and lymph node status in breast cancer”. Asian Pac J Cancer Prev 9(4) (2008), pp. 553–556.
Bing Song et al. “Targeting FOXA1-mediated repression of TGF-β signaling suppresses castration-resistant prostate cancer progression”. J Clin Invest 129(2) (2018), pp. 569–582. DOI: 10.1172/jci122367. DOI: https://doi.org/10.1172/JCI122367
Derek F. Amanatullah et al. “Local estrogen axis in the human bone microenvironment regulates estrogen receptor-positive breast cancer cells”. Breast Cancer Res 19(1) (2017), pp. 121–121. DOI: 10.1186/s13058-017-0910-x. DOI: https://doi.org/10.1186/s13058-017-0910-x
Esther Rheinbay et al. “Recurrent and functional regulatory mutations in breast cancer”. Nature 547(7661) (2017), pp. 55–60. DOI: 10.1038/nature22992. DOI: https://doi.org/10.1038/nature22992
G Jiang et al. “Cooperativity of co-factor NR2F2 with Pioneer Factors GATA3, FOXA1 in promoting ERα function”. Theranostics 9(22) (2019), pp. 6501–6516. DOI: 10.7150/thno.34874. DOI: https://doi.org/10.7150/thno.34874
G M Clark, C K Osborne, and W L McGuire. “Correlations between estrogen receptor, progesterone receptor, and patient characteristics in human breast cancer.” J Clin Oncol 2(10) (1984), pp. 1102–1109. DOI: 10.1200/jco.1984.2.10.1102. DOI: https://doi.org/10.1200/JCO.1984.2.10.1102
Gina M. Bernardo and Ruth A. Keri. “FOXA1: a transcription factor with parallel functions in development and cancer”. Biosci Rep 32(2) (2012), pp. 113–130. DOI: 10.1042/bsr20110046. DOI: https://doi.org/10.1042/BSR20110046
Huiyan Ma et al. “Body mass index at age 18 years and recent body mass index in relation to risk of breast cancer overall and ER/PR/HER2-defined subtypes in white women and African-American women: a pooled analysis”. Breast Cancer Res 20(1) (2018), pp. 5–6. DOI: 10.1186/s13058-017-0931-5. DOI: https://doi.org/10.1186/s13058-017-0931-5
J Laganière et al. “From the Cover: Location analysis of estrogen receptor alpha target promoters reveals that FOXA1 defines a domain of the estrogen response”. Proc Natl Acad Sci U S A 102 (2005), pp. 11651–11656. DOI: 10.1073/pnas.0505575102. DOI: https://doi.org/10.1073/pnas.0505575102
J Rosai. Rosai and Ackerman’s Surgical Pathology. Ed. by and others. 10th. Vol. 1. Elsevier Inc. Italy, 2011.
J Xu et al. “Prediction of tumor mutation burden in breast cancer based on the expression of ER, PR, HER -2 and Ki-67”. Onco Targets Ther 11 (2018), pp. 2269–2275. DOI: https://doi.org/10.2147/OTT.S159830
Jason S. Carroll et al. “Chromosome-Wide Mapping of Estrogen Receptor Binding Reveals Long-Range Regulation Requiring the Forkhead Protein FoxA1”. Cell 122(1) (2005), pp. 33–43. DOI: 10.1016/j.cell.2005.05.008. DOI: https://doi.org/10.1016/j.cell.2005.05.008
Jiafeng Shou et al. “Prognostic value of FOXA1 in breast cancer: A systematic review and meta-analysis”. Breast 27 (2016), pp. 35–43. DOI: 10.1016/j.breast.2016.02.009. DOI: https://doi.org/10.1016/j.breast.2016.02.009
Jonathan G Moggs and George Orphanides. “Estrogen receptors: orchestrators of pleiotropic cellular responses”. EMBO Rep 2(9) (2001), pp. 775–781. DOI: 10.1093/embo-reports/kve185. DOI: https://doi.org/10.1093/embo-reports/kve185
Jonna Frasor et al. “Profiling of Estrogen Up- and Down-Regulated Gene Expression in Human Breast Cancer Cells: Insights into Gene Networks and Pathways Underlying Estrogenic Control of Proliferation and Cell Phenotype”. Endocrinology 144(10) (2003), pp. 4562–4574. DOI: 10.1210/en.2003-0567. DOI: https://doi.org/10.1210/en.2003-0567
Jumaah, Sh. S. (2013). Molecular Detection of Mutations in BRCA1, BRCA2, K-Ras and PIK3CA Genes in Iraqi Breast Cancer Patients and Their Families. Ph.D. thesis. Baghdad University. Iraq. Baghdad. pp.142.
K Michailidou. “Association analysis identifies 65 new breast cancer risk loci”. Nature 551(7678) (2018), pp. 92–94. DOI: 10.1038/nature24284. DOI: https://doi.org/10.1038/nature24284
K Wang et al. “Clinical significance and prognostic value of Forkhead box A1 expression in human epithelial ovarian cancer”. Oncol Lett 15 (2018), pp. 4457–4462. DOI: 10.3892/ol.2018.7899. DOI: https://doi.org/10.3892/ol.2018.7899
KELI HE et al. “Clinicopathological significance of forkhead box protein A1 in breast cancer: A meta-analysis”. Exper Ther Med 11(6) (2016), pp. 2525–2530. DOI: 10.3892/etm.2016.3229. DOI: https://doi.org/10.3892/etm.2016.3229
L A Cirillo et al. “Binding of the winged-helix transcription factor HNF3 to a linker histone site on the nucleosome”. EMBO J 17(1) (1998), pp. 244–254. DOI: 10.1093/emboj/17.1.244. DOI: https://doi.org/10.1093/emboj/17.1.244
L Lin et al. “The hepatocyte nuclear factor 3 α gene, HNF3α (FOXA1), on chromosome band 14q13 is amplified and overexpressed in esophageal and lung adenocarcinomas”. Cancer Res 62(18) (2002), pp. 5273–5279.
LakminiK. B Mudduwa. “Quick score of hormone receptor status of breast carcinoma: Correlation with the other clinicopathological prognostic parameters”. Indian J Pathol Microbiol 52(2) (2009), pp. 159–159. DOI: 10.4103/0377-4929.48906. DOI: https://doi.org/10.4103/0377-4929.48906
Luka Bolha et al. “Comparison of methods for relative quantification of gene expression using real-time PCR”. Acta Agric Slov 100(2) (2012), pp. 97–106. DOI: 10.2478/v10014-012-0018-z. DOI: https://doi.org/10.2478/v10014-012-0018-z
M. A. Climent et al. “Prognostic value of HER-2/neu and p53 expression in node-positive breast cancer. HER-2/neu effect on adjuvant tamoxifen treatment”. Breast 10(1) (2001), pp. 67–77. DOI: 10.1054/brst.2000.0225. DOI: https://doi.org/10.1054/brst.2000.0225
Marjolein Droog et al. “Comparative Cistromics Reveals Genomic Cross-talk between FOXA1 and ERα in Tamoxifen-Associated Endometrial Carcinomas”. Cancer Res 76(13) (2016), pp. 3773–3784. DOI: 10.1158/0008-5472.can-14-1813. DOI: https://doi.org/10.1158/0008-5472.CAN-14-1813
Michael H Cho et al. “Folliculin mutations are not associated with severe COPD”. BMC Med Genet 9(1) (2008). DOI: 10.1186/1471-2350-9-120. DOI: https://doi.org/10.1186/1471-2350-9-120
N A Alwan, F N Tawfeeq, and N A Mallah. “Demographic and clinical profiles of female patients diagnosed with breast cancer in Iraq”. J Contemp Med Sci 5(1) (2019), pp. 14–19. DOI: https://doi.org/10.22317/jcms.v5i1.544
Nidal M Almasri and Mohammad Al Hamad. “Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in breast carcinoma in Jordan”. Breast Cancer Res 7(5) (2005), pp. 598–604. DOI: 10.1186/bcr1200. DOI: https://doi.org/10.1186/bcr1200
Runnak A Majid et al. “Breast cancer in Iraq is associated with a unimodally distributed predominance of luminal type B over luminal type A surrogates from young to old age”. BMC Womens Health 17(1) (2017), pp. 27–28. DOI: 10.1186/s12905-017-0376-0. DOI: https://doi.org/10.1186/s12905-017-0376-0
Rutika J. Mehta et al. “FOXA1 is an independent prognostic marker for ER-positive breast cancer”. Breast Cancer Res Treat 131(3) (2012), pp. 881–890. DOI: 10.1007/s10549-011-1482-6. DOI: https://doi.org/10.1007/s10549-011-1482-6
S De Lara et al. “The prognostic relevance of FOXA1 and Nestin expression in breast cancer metastases: a retrospective study of 164 cases during a 10-year period”. BMC Cancer 19(1) (2004), pp. 187–187. DOI: 10.1186/s12885-019-5373-2. DOI: https://doi.org/10.1186/s12885-019-5373-2
Sunil Badve et al. “FOXA1 Expression in Breast Cancer—Correlation with Luminal Subtype A and Survival”. Clin Cancer Res 13(15) (2007), pp. 4415–4421. DOI: 10.1158/1078-0432.ccr-07-0122. DOI: https://doi.org/10.1158/1078-0432.CCR-07-0122
T. Sekiya et al. “Nucleosome-binding affinity as a primary determinant of the nuclear mobility of the pioneer transcription factor FoxA”. Genes Dev 23(7) (2009), pp. 804–809. DOI: 10.1101/gad.1775509. DOI: https://doi.org/10.1101/gad.1775509
W M T Al-Nuaimy, A H Ahmed, and H A A Al-Nuaimy. “Immunohistochemical Evaluation of Triple Markers (ER, PR and HER-2/neu) in Carcinoma of the Breast in the North of Iraq”. Don J Med Lab Diagn 1(1) (2015), pp. 1–009.
X C Wu et al. “Cancer in North America, 1995-1999”. Cancer in North America III(NAACCR Combined Cancer Incidence Rates) (2002).
X Dai et al. “FOXA1 is Prognostic of Triple Negative Breast Cancers by Transcriptionally Suppressing SOD2 and IL6”. Int J Biol Sci 15(5) (2019), pp. 1030–1041. DOI: https://doi.org/10.7150/ijbs.31009
X Wang et al. “Functional Variant rs4442975 Modulating FOXA1 Binding Affinity Can Influence Bone Marrow Suppression during Neoadjuvant Chemotherapy for Luminal A Type Breast Cancer”. BioMed Res (2019). DOI: https://doi.org/10.1155/2019/7073498
Xiaoyong Fu et al. “FOXA1 overexpression mediates endocrine resistance by altering the ER transcriptome and IL-8 expression in ER-positive breast cancer”. Proc Natl Acad Sci U S A 113 (2016), E6600–E6609. DOI: 10.1073/pnas.1612835113. DOI: https://doi.org/10.1073/pnas.1612835113
Y A Yang and J Yu. “Current perspectives on FOXA1 regulation of androgen receptor signaling and prostate cancer”. Genes Dis 2 (2015), pp. 144–151. DOI: 10.1016/j.gendis.2015.01.003. DOI: https://doi.org/10.1016/j.gendis.2015.01.003
Yuichi Hisamatsu et al. “Impact of FOXA1 Expression on the Prognosis of Patients with Hormone Receptor-Positive Breast Cancer”. Ann Surg Oncol 19(4) (2012), pp. 1145–1152. DOI: 10.1245/s10434-011-2094-4. DOI: https://doi.org/10.1245/s10434-011-2094-4
Yuichi Hisamatsu et al. “Impact of GATA-3 and FOXA1 expression in patients with hormone receptor-positive/HER2-negative breast cancer”. Breast Cancer 22(5) (2015), pp. 520–528. DOI: 10.1007/s12282-013-0515-x. DOI: https://doi.org/10.1007/s12282-013-0515-x
Z Gu et al. “Clinical value of the changes of ER, PR, HER2 and Ki-67 expressions before and after neoadjuvant chemotherapy in breast cancer”. Open Sci J Clin Med 6(2) (2018), pp. 10–14.
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