{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T01:00:55Z","timestamp":1785200455184,"version":"3.55.0"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T00:00:00Z","timestamp":1646352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016714","name":"University of Sharjah","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016714","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Breast cancer (BC) is the most diagnosed cancer and the leading cause of global cancer incidence in 2020. It is quite known that highly invasive cancers have disrupted metabolism that leads to the creation of an acidic tumor microenvironment. Among the proton-sensing G protein-coupled receptors is GPR68. In this study, we aimed to explore the expression pattern of GPR68 in tissues from BC patients as well as different BC cell lines. Methods: In-silico tools were used to assess the expression of GPR68 in BC patients. The expression pattern was validated in fresh and paraffin-embedded sections of BC patients using qPCR and immunohistochemistry (IHC), respectively. Also, in-silico tools investigated GPR68 expression in different BC cell lines. Validation of GPR68 expression was performed using qPCR and immunofluorescence techniques in four different BC cell lines (MCF-7, MDA-MB-231, BT-549 and SkBr3). Results: GPR68 expression was found to be significantly increased in BC patients using the in-silico tools and validation using qPCR and IHC. Upon classification according to the molecular subtypes, the luminal subtype showed the highest GPR68 expression followed by triple-negative and Her2-enriched cells. However, upon validation in the recruited cohort, the triple-negative molecular subtype of BC patients showed the highest GPR68 expression. Also, in-silico and validation data revealed that the triple-negative breast cancer cell line MDA-MB-231 showed the highest expression of GPR68. Conclusion: Therefore, this study highlights the potential utilization of GPR68 as a possible diagnostic and\/or prognostic marker in BC.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2022.847543","type":"journal-article","created":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T05:21:44Z","timestamp":1646371304000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Expression of GPR68, an Acid-Sensing Orphan G Protein-Coupled Receptor, in Breast Cancer"],"prefix":"10.3389","volume":"12","author":[{"given":"Noha Mousaad","family":"Elemam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rana A.","family":"Youness","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amal","family":"Hussein","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israa","family":"Shihab","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nada M.","family":"Yakout","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasmine Nagy","family":"Elwany","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamer M.","family":"Manie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iman M.","family":"Talaat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azzam A.","family":"Maghazachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,3,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA: A Cancer J Clin"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation","volume":"324","author":"Vander Heiden","year":"2009","journal-title":"Sci (New York NY)"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2013.00354","article-title":"Acidic Tumor Microenvironment and pH-Sensing G Protein-Coupled Receptors","volume":"4","author":"Justus","year":"2013","journal-title":"Front Physiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1846","DOI":"10.1158\/1538-7445.AM2019-1846","article-title":"Abstract 1846: Acid Sensing G Protein-Coupled Receptor OGR1 is Required for Acid Induced Adiposomogenesis in Breast Cancer Cells","volume":"79","author":"Pillai","year":"2019","journal-title":"Cancer Res"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3110","article-title":"Dysregulated Ph: A Perfect Storm for Cancer Progression","volume":"11","author":"Webb","year":"2011","journal-title":"Nat Rev Cancer"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-1743","article-title":"Neutralization of Tumor Acidity Improves Antitumor Responses to Immunotherapy","volume":"76","author":"Pilon-Thomas","year":"2016","journal-title":"Cancer Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.Can-07-5575","article-title":"Bicarbonate Increases Tumor pH and Inhibits Spontaneous Metastases","volume":"69","author":"Robey","year":"2009","journal-title":"Cancer Res"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.juro.2012.03.113","article-title":"Systemic Buffers Inhibit Carcinogenesis in TRAMP Mice","volume":"188","author":"Ibrahim-Hashim","year":"2012","journal-title":"J Urol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0230374100","article-title":"The G Protein-Coupled Receptor Repertoires of Human and Mouse","volume":"100","author":"Vassilatis","year":"2003","journal-title":"Proc Natl Acad Sci U.S.A."},{"key":"B10","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/nrd.2016.230","article-title":"A Comprehensive Map of Molecular Drug Targets","volume":"16","author":"Santos","year":"2017","journal-title":"Nat Rev Drug Discov"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1124\/mol.117.111062","article-title":"Insel PA. 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