{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T09:05:19Z","timestamp":1790672719074,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009606","name":"Arabian Gulf University","doi-asserted-by":"publisher","award":["G2-AGU-11-23"],"award-info":[{"award-number":["G2-AGU-11-23"]}],"id":[{"id":"10.13039\/100009606","id-type":"DOI","asserted-by":"publisher"}]},{"award":["G2-AGU-11-23"],"award-info":[{"award-number":["G2-AGU-11-23"]}],"id":[{"id":"https:\/\/ror.org\/04gd4wn47","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: PAPSS1 (3\u2032-Phosphoadenosine 5\u2032-Phosphosulfate Synthase 1) plays a central role in the sulfation process that regulates estrogen activity; however, its pattern of expression and association with clinicopathological features in breast carcinoma (BC) are not fully examined. Methods: A total of 150 BC specimens with clinicopathological and 10-year follow-up data were analyzed. PAPSS1 protein expression was assessed using immunohistochemistry (IHC) and correlated with clinicopathological parameters and patient outcome. Transcriptomic and promotor methylation analyses were performed using TCGA-BRCA through UALCAN. Proteomic data was evaluated using the CPTAC dataset, and the gene interaction network was analyzed using STRING. Results: IHC demonstrated significantly higher PAPSS1 expression in invasive carcinomas compared with non-invasive carcinoma and with normal mammary acini (p &lt; 0.0001). High expression was associated with the presence of vascular invasion (VI) (p = 0.003), LN metastasis (p = 0.008), and higher PAPSS1 expression in tumor capillaries (p &lt; 0.001). CPTAC analyses confirmed significantly elevated PAPSS1 in tumors versus normal tissues (p &lt; 0.0001), particularly in stage II and III tumors, triple-negative BC, and basal stromal-related molecular subtypes. The transcriptomic data showed different expression patterns according to tissue type; it is higher in GIT tumors. The opposite was found in lung and pancreatic carcinoma. In BC, transcriptional expression was not different between normal and tumors; it was lower in higher nodal stages and highest in medullary carcinoma and in TP53-mutant tumors. Conclusions: PAPSS1 is overexpressed in BC and is associated with VI, LN metastasis, and tumor progression, suggesting a potential role in BC aggressiveness. Further studies are recommended to explore its mechanistic role.<\/jats:p>","DOI":"10.3390\/cancers18193143","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:12:42Z","timestamp":1790669562000},"page":"3143","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond Sulfation: Integrated Immunohistochemical, Genomic, and Proteomic Profiling Identifies PAPSS1 as a Potential Regulator of Breast Cancer Progression"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4088-8417","authenticated-orcid":false,"given":"Rabab Ahmed Ahmed","family":"Mohammed","sequence":"first","affiliation":[{"name":"Department of Pathology, College of Medicine and Health Sciences, Arabian Gulf University, Manama 329, Bahrain"},{"name":"Department of Pathology, Faculty of Medicine, Assiut University, Assiut 71515, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5759-6130","authenticated-orcid":false,"given":"Amina","family":"Ismaeel","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine and Health Sciences, Arabian Gulf University, Manama 329, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Safa","family":"Alshaikh","sequence":"additional","affiliation":[{"name":"Department of Pathology, Salmaniya Medical Complex, Manama 329, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aalaa","family":"Mubarak","sequence":"additional","affiliation":[{"name":"Department of Pathology, Salmaniya Medical Complex, Manama 329, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sajedah","family":"Sabt","sequence":"additional","affiliation":[{"name":"Department of Oncology, Salmaniya Medical Complex, Manama 329, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3658-5987","authenticated-orcid":false,"given":"Samvel","family":"Selvam","sequence":"additional","affiliation":[{"name":"Department of Pathology, College of Medicine and Health Sciences, Arabian Gulf University, Manama 329, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"ref_1","first-page":"477","article-title":"Breast cancer statistics 2024","volume":"74","author":"Giaquinto","year":"2024","journal-title":"CA Cancer J. 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