<?xml version="1.1" encoding="utf-8"?>
<article xsi:noNamespaceSchemaLocation="http://jats.nlm.nih.gov/publishing/1.1/xsd/JATS-journalpublishing1-mathml3.xsd" dtd-version="1.1" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"><front><journal-meta><journal-id journal-id-type="publisher-id">PAR</journal-id><journal-title-group><journal-title>Proceedings of Anticancer Research</journal-title></journal-title-group><issn>2208-3545</issn><eissn>2208-3553</eissn><publisher><publisher-name>Bio-Byword Scientific Publishing Pty. Ltd.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.26689/par.v8i3.6865</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title>Comprehensive Analysis of Estrogen Receptor 1 Dysregulation in Liver Hepatocellular Carcinoma: Implications for Prognosis and Therapeutic Targeting</title><url>https://artdesignp.com/journal/PAR/8/3/10.26689/par.v8i3.6865</url><author>RazaSyed Hussain,HameedYasir</author><pub-date pub-type="publication-year"><year>2024</year></pub-date><volume>8</volume><issue>3</issue><history><date date-type="pub"><published-time>2024-06-19</published-time></date></history><abstract>The study investigates the expression pattern and regulatory mechanisms of estrogen receptor 1 (ESR1) in liver hepatocellular carcinoma (LIHC) through comprehensive bioinformatics analysis. Utilizing UALCAN and GEPIA2 databases, significant down-regulation of ESR1 expression is observed in LIHC samples compared to normal controls, indicating its potential role in tumor progression. Further analysis reveals consistent down-regulation across different clinical variables including patient age, gender, race, and various stages of LIHC, affirming the regulatory role of ESR1 in tumor development and progression. Additionally, promoter methylation analysis demonstrates hypermethylation of ESR1 in LIHC samples, negatively correlating with its expression. This association persists across different clinical parameters, emphasizing the inverse relationship between ESR1 methylation and expression levels. Survival analysis indicates that up-regulation of ESR1 is associated with better overall survival, suggesting its potential as a prognostic biomarker in LIHC. Furthermore, genetic mutation analysis using cBioPortal reveals a spectrum of alterations in ESR1, including amplification, missense mutation, deep deletion, splice mutation, and truncating mutation, highlighting the genetic complexity of ESR1 in LIHC. These findings collectively contribute to a deeper understanding of ESR1 dysregulation in LIHC and its clinical implications as a potential therapeutic target and prognostic marker.</abstract><keywords/></article-meta></front><body/><back><ref-list><ref id="B1" content-type="article"><label>1</label><element-citation publication-type="journal"><p>Krieghoff-Henning E, Folkerts J, Penzkofer AS, et al., 2017, Cancer – An Overview. Med Monatsschr Pharm, 40(2): 48–54.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B2" content-type="article"><label>2</label><element-citation publication-type="journal"><p>Bray F, Laversanne M, Sung H, et al., 2024, Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 74(3): 229–263.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B3" content-type="article"><label>3</label><element-citation publication-type="journal"><p>Upadhyay A, 2021, Cancer: An Unknown Territory; Rethinking Before Going Ahead. Genes Dis, 8(5): 655–661.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B4" content-type="article"><label>4</label><element-citation publication-type="journal"><p>Kaur H, Bhalla S, Raghava GPS, 2019, Classification of Early and Late Stage Liver Hepatocellular Carcinoma Patients from Their Genomics and Epigenomics Profiles. PLoS One, 14(9): e0221476.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B5" content-type="article"><label>5</label><element-citation publication-type="journal"><p>Gao S, Gang J, Yu M, et al., 2021, Computational Analysis for Identification of Early Diagnostic Biomarkers and Prognostic Biomarkers of Liver Cancer Based on GEO and TCGA Databases and Studies on Pathways and Biological Functions Affecting the Survival Time of Liver Cancer. BMC Cancer, 2021(21): 1–15.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B6" content-type="article"><label>6</label><element-citation publication-type="journal"><p>Sung H, Ferlay J, Siegel RL, et al., 2021, Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71(3): 209–249.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B7" content-type="article"><label>7</label><element-citation publication-type="journal"><p>Balogh J, Victor III D, Asham EH, et al., 2016, Hepatocellular Carcinoma: A Review. Journal of Hepatocellular Carcinoma, (2016): 41–53.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B8" content-type="article"><label>8</label><element-citation publication-type="journal"><p>Zhou H, Song T, 2021, Conversion Therapy and Maintenance Therapy for Primary Hepatocellular Carcinoma. BioScience Trends, 15(3): 155–160.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B9" content-type="article"><label>9</label><element-citation publication-type="journal"><p>Long J, Lin J, Wang A, et al., 2017, PD-1/PD-L Blockade in Gastrointestinal Cancers: Lessons Learned and the Road Toward Precision Immunotherapy. Journal of Hematology &amp; Oncology, (10): 1–21.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B10" content-type="article"><label>10</label><element-citation publication-type="journal"><p>Poon D, Anderson BO, Chen LT, et al., 2009, Management of Hepatocellular Carcinoma in Asia: Consensus Statement from the Asian Oncology Summit 2009. The Lancet Oncology, 10(11): 1111–1118.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B11" content-type="article"><label>11</label><element-citation publication-type="journal"><p>Huang A, Yang XR, Chung WY, et al., 2020, Targeted Therapy for Hepatocellular Carcinoma. Signal Transduction and Targeted Therapy, 5(1): 146.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B12" content-type="article"><label>12</label><element-citation publication-type="journal"><p>Hofmann WK, 2006, Gene Expression Profiling by Microarrays: Clinical Implications, Cambridge University Press, Cambridge.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B13" content-type="article"><label>13</label><element-citation publication-type="journal"><p>Higa GM, Fell RG, 2013, Sex Hormone Receptor Repertoire in Breast Cancer. International Journal of Breast Cancer, (2013): 284036.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B14" content-type="article"><label>14</label><element-citation publication-type="journal"><p>Huang B, Warner M, Gustafsson JÅ, 2015, Estrogen Receptors in Breast Carcinogenesis and Endocrine Therapy. Molecular and Cellular Endocrinology, (418): 240–244.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B15" content-type="article"><label>15</label><element-citation publication-type="journal"><p>De Santo I, McCartney A, Migliaccio I, et al., 2019, The Emerging Role of ESR1 Mutations in Luminal Breast Cancer as a Prognostic and Predictive Biomarker of Response to Endocrine Therapy. Cancers (Basel), 11(12): 1894.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B16" content-type="article"><label>16</label><element-citation publication-type="journal"><p>Bhat M, Pasini E, Pastrello C, et al., 2021, Estrogen Receptor 1 Inhibition of Wnt/?-Catenin Signaling Contributes to Sex Differences in Hepatocarcinogenesis. Front Oncol, (11): 777834.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B17" content-type="article"><label>17</label><element-citation publication-type="journal"><p>Liang J, Lv J, Liu Z, 2015, Identification of Dysfunctional Biological Pathways and Their Synergistic Mechanism in Hepatocellular Carcinoma Process. Experimental and Molecular Pathology, 98(3): 540–545.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B18" content-type="article"><label>18</label><element-citation publication-type="journal"><p>Hishida M, Nomoto S, Inokawa Y, et al., 2013, Estrogen Receptor 1 Gene as a Tumor Suppressor Gene in Hepatocellular Carcinoma Detected by Triple-Combination Array Analysis. International journal of oncology, 43(1): 88–94.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B19" content-type="article"><label>19</label><element-citation publication-type="journal"><p>Zundelevich A, Dadiani M, Kahana-Edwin S, et al., 2020, ESR1 Mutations are Frequent in Newly Diagnosed Metastatic and Loco-Regional Recurrence of Endocrine-Treated Breast Cancer and Carry Worse Prognosis. Breast Cancer Research, 22(1): 16.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B20" content-type="article"><label>20</label><element-citation publication-type="journal"><p>Merenbakh-Lamin K, Ben-Baruch N, Yeheskel A, et al., 2013, D538G Mutation in Estrogen Receptor-?: A Novel Mechanism for Acquired Endocrine Resistance in Breast Cancer. Cancer Research, 73(23): 6856–6864.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B21" content-type="article"><label>21</label><element-citation publication-type="journal"><p>Jeselsohn R, Yelensky R, Buchwalter G, et al., 2014, Emergence of Constitutively Active Estrogen Receptor-? Mutations in Pretreated Advanced Estrogen Receptor–Positive Breast Cancer. Clinical Cancer Research, 20(7): 1757–1767.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B22" content-type="article"><label>22</label><element-citation publication-type="journal"><p>Toy W, Shen Y, Won H, et al., 2013, ESR1 Ligand-Binding Domain Mutations in Hormone-Resistant Breast Cancer. Nature Genetics, 45(12): 1439–1445.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B23" content-type="article"><label>23</label><element-citation publication-type="journal"><p>Gelsomino L, Gu G, Rechoum Y, et al., 2016, ESR1 Mutations Affect Anti-Proliferative Responses to Tamoxifen Through Enhanced Cross-Talk with IGF Signaling. Breast Cancer Research and Treatment, (157): 253–265.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B24" content-type="article"><label>24</label><element-citation publication-type="journal"><p>Toy W, Weir H, Razavi P, et al., 2017, Activating ESR1 Mutations Differentially Affect the Efficacy of ER Antagonists. Cancer Discovery, 7(3): 277–287.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B25" content-type="article"><label>25</label><element-citation publication-type="journal"><p>Chandrashekar DS, Bashel B, Balasubramanya SAH, et al., 2017, UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia, 19(8): 649–658.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B26" content-type="article"><label>26</label><element-citation publication-type="journal"><p>Tang Z, Li C, Kang B, et al., 2017, GEPIA: A Web Server for Cancer and Normal Gene Expression Profiling and Interactive Analyses. Nucleic Acids Research, 45(W1): W98–W102.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B27" content-type="article"><label>27</label><element-citation publication-type="journal"><p>Gy?rffy B, Surowiak P, Budczies J, et al., 2013, Online Survival Analysis Software to Assess the Prognostic Value of Biomarkers Using Transcriptomic Data in Non-Small-Cell Lung Cancer. PLoS One, 8(12): e82241.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B28" content-type="article"><label>28</label><element-citation publication-type="journal"><p>Cerami E, Gao J, Dogrusoz U, et al., 2012, The cBio Cancer Genomics Portal: An Open Platform for Exploring Multidimensional Cancer Genomics Data. Cancer Discovery, 2(5): 401–404.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B29" content-type="article"><label>29</label><element-citation publication-type="journal"><p>Luczak MW, Jagodzi?ski PP, 2006, The Role of DNA Methylation in Cancer Development. Folia Histochem Cytobiol, 44(3): 143–154.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B30" content-type="article"><label>30</label><element-citation publication-type="journal"><p>Estes C, Razavi H, Loomba R, et al., 2018, Modeling the Epidemic of Nonalcoholic Fatty Liver Disease Demonstrates an Exponential Increase in Burden of Disease. Hepatology, 67(1): 123–133.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B31" content-type="article"><label>31</label><element-citation publication-type="journal"><p>Usman M, Hameed Y, 2022, GNB1, a Novel Diagnostic and Prognostic Potential Biomarker of Head and Neck and Liver Hepatocellular Carcinoma. Journal of Cancer Research and Therapeutics, 20(2).</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B32" content-type="article"><label>32</label><element-citation publication-type="journal"><p>Chandrashekar DS, Bashel B, Balasubramanya SAH, et al., 2017, UALCAN: A Portal for Facilitating Tumor Subgroup Gene Expression and Survival Analyses. Neoplasia, 19(8): 649–658.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B33" content-type="article"><label>33</label><element-citation publication-type="journal"><p>McCleary-Wheeler AL, Lomberk GA, Weiss FU, et al., 2013, Insights into the Epigenetic Mechanisms Controlling Pancreatic Carcinogenesis. Cancer Lett, 328(2): 212–221.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B34" content-type="article"><label>34</label><element-citation publication-type="journal"><p>Usman M, Hameed Y, Ahmad M, et al., 2022, Breast Cancer Risk and Human Papillomavirus Infection: A Bradford Hill Criteria Based Evaluation. Infect Disord Drug Targets, 22(4): e200122200389.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B35" content-type="article"><label>35</label><element-citation publication-type="journal"><p>Hameed Y, Usman M, Liang S, et al., 2021, Novel Diagnostic and Prognostic Biomarkers of Colorectal Cancer: Capable to Overcome the Heterogeneity-Specific Barrier and Valid for Global Applications. PLoS One, 16(9): e0256020.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B36" content-type="article"><label>36</label><element-citation publication-type="journal"><p>Zhang L, Sahar AM, Li C, et al., 2022, A Detailed Multi-Omics Analysis of GNB2 Gene in Human Cancers. Braz J Biol, (84): e260169.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B37" content-type="article"><label>37</label><element-citation publication-type="journal"><p>Välk K, Vooder T, Kolde R, et al., 2010, Gene Expression Profiles of Non-Small Cell Lung Cancer: Survival Prediction and New Biomarkers. Oncology, 79(3–4): 283–292.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B38" content-type="article"><label>38</label><element-citation publication-type="journal"><p>Jenssen TK, Kuo WP, Stokke T, et al., 2002, Associations Between Gene Expressions in Breast Cancer and Patient Survival. Hum Genet, 111(4–5): 411–420.</p><pub-id pub-id-type="doi"/></element-citation></ref></ref-list></back></article>
