{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T18:24:06Z","timestamp":1776709446449,"version":"3.51.2"},"reference-count":53,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T00:00:00Z","timestamp":1709078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["GO 3055\/4-1"],"award-info":[{"award-number":["GO 3055\/4-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["HO 1875\/27-1"],"award-info":[{"award-number":["HO 1875\/27-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RA 2151\/5-1"],"award-info":[{"award-number":["RA 2151\/5-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RA 2151\/7-1"],"award-info":[{"award-number":["RA 2151\/7-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002957","name":"Technische Universit\u00e4t Dresden","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002957","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arch Gynecol Obstet"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Leucine-rich \u03b1-2 glycoprotein 1 (LRG-1) is a secreted glycoprotein that is mainly produced in the liver. Elevated levels of LRG-1 are found in a multitude of pathological conditions including eye diseases, diabetes, infections, autoimmune diseases, and cancer. In patients with early breast cancer (BC), high intratumoral LRG-1 protein expression levels are associated with reduced survival. In this study, we assessed serum levels of LRG-1 in patients with early BC and investigated its correlation with the presence of disseminated tumor cells (DTCs) in the bone marrow and survival outcomes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Serum LRG-1 levels of 509 BC patients were determined using ELISA and DTCs were assessed by immunocytochemistry using the pan-cytokeratin antibody A45-B\/B3. We stratified LRG-1 levels according to selected clinical parameters. Using the log-rank (Mantel\u2013Cox) test and multivariate Cox regression analysis, Kaplan\u2013Meier survival curves and prognostic relevance were assessed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Mean serum levels of LRG-1 were 29.70\u2009\u00b1\u20098.67\u00a0\u00b5g\/ml. Age was positively correlated with LRG-1 expression (r\u2009=\u20090.19; p\u2009&lt;\u20090.0001) and significantly higher LRG-1 levels were found in patients over 60\u00a0years compared to younger ones (30.49\u2009\u00b1\u20098.63\u00a0\u00b5g\/ml vs. 28.85\u2009\u00b1\u20098.63\u00a0\u00b5g\/ml; p\u2009=\u20090.011) and in postmenopausal patients compared to premenopausal patients (30.15\u2009\u00b1\u20098.34\u00a0\u00b5g\/ml vs. 26.936.94\u00a0\u00b5g\/ml; p\u2009=\u20090.002). Patients with no DTCs showed significantly elevated LRG-1 levels compared to the DTC-positive group (30.51\u2009\u00b1\u20098.69\u00a0\u00b5g\/ml vs. 28.51\u2009\u00b1\u20098.54\u00a0\u00b5g\/ml; p\u2009=\u20090.004). Overall and BC-specific survival was significantly lower in patients with high serum LRG-1 levels (above a cut-off of 33.63\u00a0\u00b5g\/ml) compared to patients with lower LRG-1 levels during a mean follow-up of 8.5\u00a0years (24.8% vs. 11.1% BC-specific death; p\u2009=\u20090.0003; odds ratio 2.63, 95%CI: 1.56\u20144.36). Multivariate analyses revealed that LRG-1 is an independent prognostic marker for BC-specific survival (p\u2009=\u20090.001; hazard ratio 2.61).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>This study highlights the potential of LRG-1 as an independent prognostic biomarker in patients with early BC.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00404-024-07434-0","type":"journal-article","created":{"date-parts":[[2024,2,28]],"date-time":"2024-02-28T04:33:11Z","timestamp":1709094791000},"page":"2789-2798","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["High serum levels of leucine-rich \u03b1-2 glycoprotein 1 (LRG-1) are associated with poor survival in patients with early breast cancer"],"prefix":"10.1007","volume":"309","author":[{"given":"Andy","family":"G\u00f6bel","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tilman D.","family":"Rachner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel Martin","family":"Klotz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabine","family":"Kasimir-Bauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rainer","family":"Kimmig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenz C.","family":"Hofbauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann-Kathrin","family":"Bittner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2024,2,28]]},"reference":[{"key":"7434_CR1","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1073\/pnas.82.7.1906","volume":"82","author":"N Takahashi","year":"1985","unstructured":"Takahashi N, Takahashi Y, Putnam FW (1985) Periodicity of leucine and tandem repetition of a 24-amino acid segment in the primary structure of leucine-rich alpha 2-glycoprotein of human serum. 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The authors have received honoraria, unrestricted educational grants and research funding from to the individual or the institution by Alexion (LCH), Amgen (AKB, LCH, OH), Ascendis (LCH), Astra Zeneca (AKB, OH), Daiichi Sankyo (AKB, OH), Eisai (OH), Gilead (AKB, OH), Hexal (AKB, OH), MSD (OH), Novartis (AKB, OH), Pharmacosmos (LCH), Pfizer (AKB, OH), Riemser (OH), Roche (OH), Seagen (OH), and UCB (LCH). All other authors declare no potential conflicts of interest.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and\/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Samples of patients were obtained before therapy after written informed consent from all subjects using protocols approved by the clinical ethic committee of the University Hospital.Essen (05\/2856).","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}