{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:17:46Z","timestamp":1785449866856,"version":"3.56.0"},"reference-count":67,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272935"],"award-info":[{"award-number":["82272935"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2026,5]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Retroperitoneal sarcoma (RPS) is a type of malignant tumour arising from mesenchymal tissues within the retroperitoneal space. RPSs tend to develop covertly and are often undiscovered when they have already grown significantly and invaded surrounding tissues and organs. These malignancies demonstrate high recurrence rates, present surgical challenges and exhibit limited responsiveness to radiotherapy and chemotherapy. Serum\u2010derived molecules are known to play critical roles in tumourigenesis and tumour progression. However, the serum molecular profile of RPS patients remains unclear.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We performed multi\u2010omics analysis of serum samples from patients with retroperitoneal dedifferentiated liposarcoma. Prolactin concentrations were quantified using Enzyme\u2010Linked Immunosorbent Assay (ELISA). RNA\u2010seq facilitated the identification of candidate signalling pathways, while gene expression was validated through quantitative polymerase chain reaction, immunohistochemistry and western blot analyses. Molecular mechanisms underlying transcriptional regulation were investigated through Chromatin Immunoprecipitation\u2010qPCR (ChIP\u2010qPCR) and dual\u2010luciferase reporter gene assays.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Integrative multi\u2010omics profiling identified significant perturbations in galactose metabolism coupled with marked elevation of prolactin (PRL) levels in Retroperitoneal Liposarcoma\u00a0(RLPS) patients. Further screening of serum prolactin levels in 100 patients with retroperitoneal tumours revealed that 90% of the cases exhibited hyperprolactinaemia in our research cohort, encompassing both malignant sarcomas and benign tumours. Studies at the clinical sample, cellular and animal levels have found that abnormally elevated prolactin in the serum can originate from sarcoma tissues. Mechanistic investigations identified SRY\u2010box transcription factor 4 (SOX4) as a previously unrecognised transcriptional regulator of PRL. Functionally, PRL not only enhanced liposarcoma cell and fibrosarcoma cell proliferation but also conferred resistance to MDM2 inhibitors. Signalling pathway analysis revealed that PRL activates the Janus Kinase\u2013Signal Transducer and Activator of Transcription Pathway (JAK\u2013STAT) signalling pathway and up\u2010regulates c\u2010MYC expression.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This study indicates that PRL can serve as an oncogenic driver and therapeutic target. The identification of SOX4\u2013PRL\u2013c\u2010MYC signalling axis provides actionable insights for developing novel therapeutic strategies against this malignancy.<\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n Retroperitoneal sarcoma cells can secrete prolactin into the bloodstream, inducing hyperprolactinaemia, which subsequently triggers metabolic reprogramming, such as glucose metabolism.<\/jats:p>\n <\/jats:list-item>\n \n SOX4 can function as a transcription factor that facilitates PRL transcription.<\/jats:p>\n <\/jats:list-item>\n \n PRL can activate the JAK\u2013STAT signalling pathway by binding to PRLR on sarcoma cells, leading to the up\u2010regulation of c\u2010MYC.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ctm2.70669","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T07:15:46Z","timestamp":1777965346000},"source":"Crossref","is-referenced-by-count":1,"title":["Oncogenic driver and therapeutic target: Prolactin signalling axis in retroperitoneal sarcoma"],"prefix":"10.1002","volume":"16","author":[{"given":"Fu'an","family":"Xie","sequence":"first","affiliation":[{"name":"Cancer Research Center Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University Xiamen Fujian China"},{"name":"National Institute for Data Science in Health and Medicine Xiamen University Xiamen Fujian China"},{"name":"Xiamen University Research Center of Retroperitoneal Tumor Committee of Oncology Society of Chinese Medical Association, Xiamen University Xiamen Fujian China"},{"name":"Xiamen Treatgut Biotechnology Co., Ltd. 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