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Integr. Neurosci."],"abstract":"<jats:p>Background: Pituitary neuroendocrine tumors (PitNETs) have different cell types and levels of growth. We do not fully understand why they grow so much. Cuproptosis is a new way that copper kills cells and it is important in cancer. But, we do not know how it works in PitNETs yet. Methods: We used several methods like bulk and single-cell sequencing with machine learning to investigate cuproptosis in PitNETs. We used Weighted Gene Co-expression Network Analysis (WGCNA) and random forest to find important genes. Then, we did tests in the lab to see how these genes work. Results: Analysis of cuproptosis-related genes (CRGs) revealed significant differences in expression and immune landscapes between invasive and non-invasive PitNETs. We established CRG-based molecular subtypes and a high-performance predictive model for tumor invasiveness. Notably, regulatory factor X1 (RFX1) was identified and validated as a key regulator that suppresses tumor growth and sensitizes cells to cuproptosis. These results highlight the clinical relevance of cuproptosis in PitNET progression and suggest RFX1 as a potential therapeutic target. Conclusion: This study establishes a single-cell\u2013based molecular landscape of PitNETs and uncovers RFX1-mediated cuproptosis as a key suppressive mechanism of tumor progression. These findings not only deepen the understanding of PitNET heterogeneity but also propose RFX1 as a promising therapeutic target for PitNETs.<\/jats:p>","DOI":"10.31083\/jin49669","type":"journal-article","created":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T08:26:51Z","timestamp":1780129611000},"source":"Crossref","is-referenced-by-count":0,"title":["Single-Cell and Integrative Analyses Uncover Therapeutic Potential of RFX1-Mediated Cuproptosis in PitNETs"],"prefix":"10.31083","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2990-9986","authenticated-orcid":true,"given":"Shuangjian","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, China Pituitary Disease Registry Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 100730 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2714-492X","authenticated-orcid":true,"given":"Changqin","family":"Pu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, China Pituitary Disease Registry Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 100730 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1744-5731","authenticated-orcid":true,"given":"Congcong","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, China Pituitary Disease Registry Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 100730 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6288-1709","authenticated-orcid":true,"given":"Xuexue","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, China Pituitary Disease Registry Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 100730 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8323-6305","authenticated-orcid":true,"given":"Si","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, China Pituitary Disease Registry Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 100730 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-2905-5119","authenticated-orcid":true,"given":"Chenxin","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, China Pituitary Disease Registry Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 100730 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0230-7593","authenticated-orcid":true,"given":"Xueyou","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, 550004 Guiyang, Guizhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2080-5474","authenticated-orcid":true,"given":"Renzhi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, China Pituitary Disease Registry Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 100730 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9588-953X","authenticated-orcid":true,"given":"Mengqi","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, China Pituitary Disease Registry Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 100730 Beijing, China"},{"name":"Institute of Clinical Medicine, National Infrastructures for Translational Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 100007 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1666-2717","authenticated-orcid":true,"given":"Ming","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, China Pituitary Disease Registry Center, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 100730 Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"16242","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","unstructured":"Aflorei ED, Korbonits M. 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