{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T17:03:07Z","timestamp":1773075787870,"version":"3.50.1"},"reference-count":21,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2012,10,16]],"date-time":"2012-10-16T00:00:00Z","timestamp":1350345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Semaphorin4D (SEMA4D) has been regarded as an important protein in tumor angiogenesis, though originally identified in neurodevelopment. SEMA4D is extensively expressed in several malignant solid tumors. Nevertheless, the function and expression of SEMA4D in epithelial ovarian cancer (EOC) is as yet not well understood. The aim of this study was to investigate SEMA4D expression in EOC and evaluate its clinical\u2013pathological and prognostic significance. Immunohistochemistry was used to analyze SEMA4D expression and tumor angiogenesis-related proteins (HIF-1\u03b1 and VEGF) in tissues from 40 patients with normal ovarian epithelia and 124 EOC patients. SEMA4D was found to be expressed in 61.3% of the 124 EOC tissues, which was significantly higher than in the normal ovarian epithelia (p &lt; 0.001). SEMA4D expression correlated with HIF-1\u03b1 and VEGF closely (\u03c1 = 0.349 and 0.263, p &lt; 0.001). Positive SEMA4D staining was significantly higher in tissues from patients with low histological grade, FIGO stage III-IV, lymph node metastasis and residual disease \u22651 cm (p &lt; 0.05). In the Cox proportional hazard mode, SEMA4D expression and histologic grade were independent indicators of overall survival (OS) and progress-free survival (PFS) for EOC patients. These findings suggest that the cooperation of SEMA4D, HIF-1\u03b1, and VEGF may indicate poor prognosis for patients with EOC, thereby demonstrating that SEMA4D and its role in angiogenesis in EOC warrants further study.<\/jats:p>","DOI":"10.3390\/ijms131013264","type":"journal-article","created":{"date-parts":[[2012,10,16]],"date-time":"2012-10-16T11:36:59Z","timestamp":1350387419000},"page":"13264-13274","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Over-Expression of Semaphorin4D, Hypoxia-Inducible Factor-1\u03b1 and Vascular Endothelial Growth Factor Is Related to Poor Prognosis in Ovarian Epithelial Cancer"],"prefix":"10.3390","volume":"13","author":[{"given":"Ying","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Gynecologic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiubao","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Biotherapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Quan","family":"Hao","sequence":"additional","affiliation":[{"name":"Department of Gynecologic Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2012,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1038\/cr.2011.198","article-title":"Semaphorin signaling in angiogenesis, lymphangiogenesis and cancer","volume":"22","author":"Sakurai","year":"2012","journal-title":"Cell Res"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/nature03875","article-title":"Common mechanisms of nerve and blood vessel wiring","volume":"436","author":"Carmeliet","year":"2005","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9017","DOI":"10.1073\/pnas.0508825103","article-title":"Semaphorin 4D provides a link between axon guidance processes and tumor-induced angiogenesis","volume":"103","author":"Basile","year":"2006","journal-title":"Proc. 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