{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSCUBE1 is a secreted and cell‐surface glycoprotein characterized by an N‐terminal signal peptide, multiple epidermal growth factor–like repeats, and a CUB domain. Early studies in vascular endothelial cells revealed that SCUBE1 is expressed selectively in highly vascularized tissues and can form oligomers with a stable association to the cell surface, suggesting roles in angiogenesis, vascular development, inflammation, and thrombosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, its structural features—including a polycationic spacer region and essential N‐glycans—support its membrane tethering and its function as a co-receptor for bone morphogenetic protein (BMP) signaling, a mechanism critical for primitive hematopoiesis as demonstrated in zebrafish."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Emerging data from prostate cancer studies further indicate that exogenously expressed SCUBE1 in cancer-associated fibroblasts can attenuate pro-tumorigenic signals, highlighting its potential regulatory role in the tumor microenvironment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel with its roles in development and cellular adhesion, SCUBE1 has been widely investigated as a diagnostic and prognostic biomarker in various diseases. Elevations in SCUBE1 levels have been reported in conditions marked by platelet activation and endothelial dysfunction. For instance, increased serum concentrations have been proposed as a diagnostic marker in gastric cancer"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ", and its rise in parallel with platelet activation has been confirmed in hemodialysis patients."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, studies in psoriasis patients suggest that SCUBE1 may serve as a novel indicator of angiogenesis while correlating with disease activity"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ", and similar diagnostic potential has been explored in Crimean-Congo hemorrhagic fever."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional investigations have extended the clinical significance of SCUBE1 to cardiovascular and thrombotic disorders. Elevated levels have been associated with hypercoagulability and thrombotic risk in breast cancer"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": ", intracerebral hemorrhage"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ", and aneurysmal subarachnoid hemorrhage."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " Similar associations have been observed in gestational diabetes mellitus as a marker of placental endothelial injury"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": ", traumatic brain injury"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", and chronic kidney disease where SCUBE1 correlates with cardiovascular risk factors."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Its levels are also increased in COVID-19"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "as well as in the pericardial fluid of patients undergoing coronary artery bypass surgery"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": ", and elevated plasma SCUBE1 has demonstrated diagnostic utility in pulmonary embolism"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": "and systemic sclerosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": " Finally, in elderly patients with acute pulmonary thromboembolism, in combination with D-dimer levels and right ventricular function indices, SCUBE1 has shown predictive value for poor prognosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": " Recent reports also support SCUBE1’s involvement in the angiogenic processes of psoriasis"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": "and its role in modulating pulmonary artery smooth muscle cell behavior following acute pulmonary embolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ruey-Bing Yang, Chi Kin Domingos Ng, Scott M Wasserman, et al. 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