{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,9]],"date-time":"2026-11-09T10:25:08Z","timestamp":1794219908163,"version":"4.8.0"},"reference-count":30,"publisher":"Journal of Neurosurgery Publishing Group (JNSPG)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,1]]},"abstract":"\n OBJECTIVE<\/jats:title>\n Prolactinomas are typically benign but represent a major cause of endocrine dysfunction. However, their molecular subtypes remain undefined, and clinical implications of such subtypes are unclear. The objective of this study was to characterize the genomic subtypes of prolactinomas and evaluate associated clinicopathological and immunological features.<\/jats:p>\n <\/jats:sec>\n \n METHODS<\/jats:title>\n A retrospective analysis was conducted on 124 prolactinoma patients who underwent resection at a single center (December 2017\u2013December 2023). Tumor specimens were subjected to RNA sequencing. Tumor immune microenvironment was evaluated using the Glasgow Microenvironment Score, with stromal and immune scores. Immune cell composition was assessed through computational deconvolution algorithms. Differentially expressed genes were validated with immunohistochemistry.<\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Unsupervised clustering identified two distinct molecular subtypes. G1 (stemness subtype) was characterized by gene expression profiles associated with stemness, including\n SOX2<\/jats:italic>\n ,\n SOX9<\/jats:italic>\n ,\n S100B<\/jats:italic>\n ,\n WNT1<\/jats:italic>\n ,\n WNT5A<\/jats:italic>\n ,\n GAL<\/jats:italic>\n ,\n CCKBR<\/jats:italic>\n ,\n STAT5A<\/jats:italic>\n ,\n STAT6<\/jats:italic>\n , and\n MAPK14<\/jats:italic>\n . These tumors exhibited a robust immune microenvironment, evidenced by high Glasgow microenvironment, stromal, and immune scores. The other subtype, G2 (proliferative subtype), was defined by elevated expression of proliferation-related genes such as\n POU1F1<\/jats:italic>\n ,\n PRL<\/jats:italic>\n ,\n TP53AIP1<\/jats:italic>\n ,\n CCND1<\/jats:italic>\n ,\n CDK6<\/jats:italic>\n ,\n ALCAM<\/jats:italic>\n ,\n GNAI1<\/jats:italic>\n ,\n SLC1A1<\/jats:italic>\n ,\n ANGPT1<\/jats:italic>\n , and\n CDKL5<\/jats:italic>\n and showed minimal immune infiltration. Clinically, G1 tumors were smaller, associated with lower preoperative prolactin levels, and displayed less aggressive behavior. In contrast, G2 tumors were larger, had significantly higher preoperative prolactin levels, and exhibited more aggressive features. All observed differences were statistically significant (p < 0.05).\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS<\/jats:title>\n Genomic profiling revealed two distinct prolactinoma subtypes\u2014stemness (G1) and proliferative (G2)\u2014with divergent immune landscapes and clinical behaviors. These findings offer a foundation for molecularly informed, individualized therapeutic strategies.<\/jats:p>\n <\/jats:sec>","DOI":"10.3171\/2026.1.jns251768","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:01:02Z","timestamp":1782259262000},"page":"671-681","source":"Crossref","is-referenced-by-count":0,"title":["Immune and clinicopathological features of molecularly defined prolactinoma subtypes"],"prefix":"10.3171","volume":"145","author":[{"given":"Da Peng","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai;"},{"name":"Department of Neurosurgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan Ting","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu Ting","family":"Dai","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Research Unit of Hematologic Malignancies Genomics and Translational Research of Chinese Academy of Medical Sciences, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De Sheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi Jun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shao Jian","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xue","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Pathology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe Bao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Center of Pituitary Tumor, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1754","reference":[{"issue":"16","key":"b1","series-title":"JAMA","first-page":"1386","article-title":"Diagnosis and management of pituitary adenomas: a review","volume":"329","author":"Tritos NA","year":"2023","unstructured":"Tritos NA, Miller KK. 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