{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T12:58:37Z","timestamp":1785329917202,"version":"3.55.0"},"reference-count":32,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background: ER\u03b2 is an estrogen receptor isoform expressed in the normal human colon and has been proposed to act as a tumor suppressor gene. The loss of ER\u03b2 expression has been associated with advanced stages of CRC. The aim was to investigate the relationship between ER\u03b2 expression and CRC progression, quantifying the difference between tumor tissues and normal controls, and early-stage versus late-stage tumors. Methods: English Medical literature searches were conducted using PubMed, Embase, and Google Scholar up to 31 December 2025 according to PRISMA. Case\u2013control studies comparing ER\u03b2 expression in CRC biopsy specimens with that in healthy controls were included. A meta-analysis was performed using Comprehensive Meta-analysis (Version 4). Pooled ORs and 95% confidence intervals were calculated using a random-effects model. Heterogeneity was assessed using the Cochrane Q test and the I2 statistic. Publication bias was evaluated. Results: Six studies, representing 13 sub-studies, were selected according to the inclusion criteria, involving 1183 patients and 1000 normal mucosa\/tumor early-stage patients. The OR for ER\u03b2 expression was 0.211 (95%CI: 0.122\u20130.363), significantly lower in advanced tumor stages than in normal mucosa and early tumor stages (p &lt; 0.0001). Positivity rates were 76.40% in controls and early-stage tumor patients versus 51.31% in tumor patients (all stages). Heterogeneity was high (I2 = 78%), but sensitivity analysis confirmed the robustness of the results. Publication bias was not significant. The studies used different methods and positivity cut-off values, with high heterogeneity, and were from only five countries, indicating the possibility of variation in results across other geographical areas or ethnic groups. Conclusions: ER\u03b2 expression is significantly lower in CRC tissues than in healthy controls and progressively decreases as the disease progresses. This finding underscores ER\u03b2\u2019s potential role as a prognostic factor and highlights the viability of ER\u03b2 activation as a novel therapeutic strategy.<\/jats:p>","DOI":"10.3390\/jcm15155924","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T11:45:14Z","timestamp":1785325514000},"page":"5924","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Estrogen Receptor Beta (ER\u03b2) Expression in Colorectal Cancer (CRC)\u2014A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"15","author":[{"given":"Yael","family":"Sher","sequence":"first","affiliation":[{"name":"Adelson Faculty of Medicine, Ariel University, Ariel 40700, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaron","family":"Niv","sequence":"additional","affiliation":[{"name":"Adelson Faculty of Medicine, Ariel University, Ariel 40700, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-3127-9_1","article-title":"The estrogen receptors: An overview from different perspectives","volume":"1366","author":"Eyster","year":"2016","journal-title":"Methods Mol. 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