<?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.v9i5.11995</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title>Thyroid Hormones in Prostate Cancer: A Systematic Review and Bibliometric Study</title><url>https://artdesignp.com/journal/PAR/9/5/10.26689/par.v9i5.11995</url><author>WuJinhai,ZhuXuejin,ChenYanfei,LiJing,WangBin</author><pub-date pub-type="publication-year"><year>2025</year></pub-date><volume>9</volume><issue>5</issue><history><date date-type="pub"><published-time>2025-10-14</published-time></date></history><abstract>Prostate cancer (PCa) is a prevalent malignancy in men, traditionally linked to androgen receptor signaling. Emerging evidence suggests thyroid hormones (THs, particularly T3/T4) play a complex role in PCa biology. THs regulate gene transcription via nuclear receptors TRα/β, modulating proliferation, apoptosis, and AR signaling, while non-genomic pathways through integrin αvβ3 activate MAPK/PI3K–Akt signaling, driving metabolic reprogramming, migration, and angiogenesis. Local DIO enzymes fine-tune T3/T4 levels, with DIO2 enhancing proliferation and DIO3 creating a low-TH microenvironment to facilitate immune evasion. Epidemiological studies associate hyperthyroidism or low TSH with elevated PCa risk, whereas experimental models show inconsistent effects, reflecting regulation by hormone levels, receptor distribution, and tumor molecular features. Bibliometric analyses reveal a shift from epidemiological studies to molecular, immune, and metabolic mechanistic research, though clinical translation remains limited. This review synthesizes current knowledge on THs in PCa, highlighting mechanistic insights, evidence gaps, and future directions, aiming to inform early detection, stratification, and therapeutic strategies.</abstract><keywords/></article-meta></front><body/><back><ref-list><ref id="B1" content-type="article"><label>1</label><element-citation publication-type="journal"><p>Wagle N, Nogueira L, Devasia T, et al., 2025, Cancer Treatment and Survivorship Statistics, 2025. CA: A Cancer Journal for Clinicians, 75: 308–340.</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>Tsamouri M, Libertini S, Siddiqui S, et al., 2025, Alteration in Expression and Subcellular Localization of the Androgen Receptor-Regulated FAM111A Protease Is Associated With Emergence of Castration Resistant Prostate Cancer. Neoplasia, 66: 101181.</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>Krashin E, Piekiełko-Witkowska A, Ellis M, et al., 2019, Thyroid Hormones and Cancer: A Comprehensive Review of Preclinical and Clinical Studies. Frontiers in Endocrinology, 10: 59.</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>Sabatino L, Vassalle C, Seppia C, et al., 2021, Deiodinases and the Three Types of Thyroid Hormone Deiodination Reactions. Endocrinology and Metabolism (Seoul), 36(5): 952–964.</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>Conde S, Luvizotto R, Síbio M, et al., 2008, Tamoxifen Inhibits Transforming Growth Factor-Alpha Gene Expression in Human Breast Carcinoma Samples Treated With Triiodothyronine. Journal of Endocrinological Investigation, 31: 1047–1051.</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>Lin H, Chin Y, Nana A, et al., 2016, Actions of L-Thyroxine and Nano-Diamino-Tetrac (Nanotetrac) on PD-L1 in Cancer Cells. Steroids, 114: 59–67.</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>Ko A, Wang F, Holly E, 2007, Pancreatic Cancer and Medical History in a Population-Based Case-Control Study in the San Francisco Bay Area, California. Cancer Causes &amp; Control, 18: 809–819.</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>Hercbergs A, Mason J, Reddy C, et al., 2004, Thyroid Hormones and Lung Cancer: Primary Hypothyroidism Is Prognostically Significant for Survival in Lung Cancer. Cancer Research, 64(3): 1024.</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>Lehrer S, Diamond E, Stone N, et al., 2005, Serum Thyroid-Stimulating Hormone Is Elevated in Men With Gleason 8 Prostate Cancer. BJU International, 96(3): 328–329.</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>Mondul A, Weinstein S, Bosworth T, et al., 2012, Circulating Thyroxine, Thyroid-Stimulating Hormone, and Hypothyroid Status and the Risk of Prostate Cancer. PLoS One, 7(10): e47730.</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>Delgado-González E, Sánchez-Tusie A, Morales G, et al., 2016, Triiodothyronine Attenuates Prostate Cancer Progression Mediated by β-Adrenergic Stimulation. Molecular Medicine, 22: 1–11.</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>Sánchez-Tusie A, Montes O, Rodríguez-Castelán J, et al., 2020, A Rise in T3/T4 Ratio Reduces the Growth of Prostate Tumors in a Murine Model. Journal of Endocrinology, 247(3): 225–238.</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>Anguiano B, Montes O, Delgado-González E, et al., 2022, Prostate Gland as a Target Organ of Thyroid Hormones: Advances and Controversies. Endocrine Connections, 11(2): e210581.</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>Groeneweg S, Geest F, Peeters R, et al., 2020, Thyroid Hormone Transporters. Endocrine Reviews, 41: bnz008.</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>Aksoy O, Pencik J, Hartenbach M, et al., 2021, Thyroid and Androgen Receptor Signaling Are Antagonized by μ-Crystallin in Prostate Cancer. International Journal of Cancer, 148: 731–747.</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>López-Juárez A, Delgado G, Aceves C, et al., 2009, Type 1 Deiodinase Activity and Generation of Triiodothyronine (T3) in Prostate of Sexually Active Rats. The Prostate, 69(15): 1651–1659.</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>Luongo C, Dentice M, Salvatore D, 2019, Deiodinases and Their Intricate Role in Thyroid Hormone Homeostasis. Nature Reviews Endocrinology, 15(8): 479–488.</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>Sakurai A, Nakai A, DeGroot L, 1989, Expression of Three Forms of Thyroid Hormone Receptor in Human Tissues. Molecular Endocrinology, 3(2): 392–399.</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>Hsieh M, Juang H, 2005, Cell Growth Effects of Triiodothyronine and Expression of Thyroid Hormone Receptor in Prostate Carcinoma Cells. Journal of Andrology, 26(3): 422–428.</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>Torabinejad S, Miro C, Barone B, et al., 2023, The Androgen-Thyroid Hormone Crosstalk in Prostate Cancer and the Clinical Implications. European Thyroid Journal, 12(3): e220228.</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>Hellevik A, Asvold B, Bjøro T, et al., 2009, Thyroid Function and Cancer Risk: A Prospective Population Study. Cancer Epidemiology, Biomarkers &amp; Prevention, 18(2): 570–574.</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>Chan Y, Knuiman M, Divitini M, et al., 2017, Lower TSH and Higher Free Thyroxine Predict Incidence of Prostate but Not Breast, Colorectal or Lung Cancer. European Journal of Endocrinology, 177: 297–308.</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>Wu J, Chen S, Xu R, et al., 2025, Multidimensional Investigation of Thyroid Hormones and Prostate Cancer: Insights From NHANES, Mendelian Randomization, Genetic Markers, and Bioinformatics Analyses. Discover Oncology, 16(1): 843.</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>Tai P, Huang Y, Shih C, et al., 2007, Direct Regulation of Androgen Receptor-Associated Protein 70 by Thyroid Hormone and Its Receptors. Endocrinology, 148(7): 3485–3495.</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>Liu Y, Yeh C, Lin K, 2019, Molecular Functions of Thyroid Hormone Signaling in Regulation of Cancer Progression and Anti-Apoptosis. International Journal of Molecular Sciences, 20(20): 4986.</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>Poplawski P, Rybicka B, Boguslawska J, et al., 2017, Induction of Type 1 Iodothyronine Deiodinase Expression Inhibits Proliferation and Migration of Renal Cancer Cells. Molecular and Cellular Endocrinology, 442: 58–67.</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>Ding X, Yang Z, 2020, Knowledge Mapping of Platform Research: A Visual Analysis Using VOSviewer and CiteSpace. Electronic Commerce Research, 1–23.</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>Eck N, Waltman L, 2010, Software Survey: VOSviewer, a Computer Program for Bibliometric Mapping. Scientometrics, 84(2): 523–538.</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>Chen C, 2006, CiteSpace II: Detecting and Visualizing Emerging Trends and Transient Patterns in Scientific Literature. Journal of the Association for Information Science and Technology, 57(3): 359–377.</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>Wickham H, 2016, ggplot2: Elegant Graphics for Data Analysis, visited on June 4, 2025, https://ggplot2.tidyverse.org.</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>D’Andréa G, Lassalle S, Guevara N, et al., 2021, From Biomarkers to Therapeutic Targets: The Promise of PD-L1 in Thyroid Autoimmunity and Cancer. Theranostics, 11(3): 1310–1325.</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>Conte K, Held F, Pipitone O, et al., 2021, The Feasibility of Recruiting and Training Lay Leaders During Real-World Program Delivery and Scale-Up: The Case of Walk With Ease. Health Promotion Practice, 22(1): 91–101.</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>Chi K, Agarwal N, Bjartell A, et al., 2019, Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. New England Journal of Medicine, 381(1): 13–24.</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>Nappi A, Miro C, Cicatiello A, et al., 2025, The Thyroid Hormone Activating Enzyme, DIO2, Is a Potential Pan-Cancer Biomarker and Immunotherapy Target. Journal of Endocrinological Investigation, 48(5): 1149–1172.</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>Patel K, Kollory A, Takashima A, et al., 2014, MicroRNA Let-7 Downregulates STAT3 Phosphorylation in Pancreatic Cancer Cells by Increasing SOCS3 Expression. Cancer Letters, 347(1): 54–64.</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, Li Q, Tang Y, et al., 2025, Co-Exposure to Bisphenol A and Arsenic Enhance Hepatotoxicity in Zebrafish by Targeting the Hypothalamic-Pituitary-Thyroid Axis and PPAR Pathway. Environmental Pollution, 384: 127037.</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>Ladanyi C, Boyd S, Sticco P, et al., 2019, Postmenopausal Endometriosis, Where Are We Now?. Current Opinion in Obstetrics &amp; Gynecology, 31(4): 267–278.</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>Bray F, Ferlay J, Soerjomataram I, et al., 2018, Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 68(6): 394–424.</p><pub-id pub-id-type="doi"/></element-citation></ref><ref id="B39" content-type="article"><label>39</label><element-citation publication-type="journal"><p>Erel C, Nigledis M, Ozcivit E, et al., 2025, Endometriosis and Menopausal Health: An EMAS Clinical Guide. Maturitas, 202: 108715.</p><pub-id pub-id-type="doi"/></element-citation></ref></ref-list></back></article>
