Abstract
Angiogenesis is an important process being involved in the pathogenesis of psoriasis and promises new potential parameter for diagnosis and screening of treatment. This study investigated the levels of signal peptide-CUB-EGF (epidermal growth factor-like protein) family domain-containing protein (SCUBE) 1 and 3. Potential value as a novel marker of angiogenesis in patients with psoriasis is also evaluated by assessing possible relation of SCUBE-1 and 3 with disease activity in conjunction with vascular endothelial growth factor (VEGF) levels, as an established marker of angiogenesis. Forty-eight patients with psoriasis (aged >18 years) and 48 age- and gender-matched healthy controls were included. Detailed information was obtained through history and physical examination. Psoriasis area and severity index (PASI) scores were calculated. Blood SCUBE 1 and 3, and VEGF levels were measured by enzyme-linked immunosorbent assay. The mean PASI score of the patients was 6.7 ± 4.1. Patients’ serum SCUBE 1 and 3 and VEGF levels were significantly higher than those of the controls (P = 0.001). The sensitivity and specificity were calculated as 83 and 62% for the 0.67 ng/ml cut-off level of SCUBE 1, and 63 and 71% for the 2.57 ng/ml cut-off level of SCUBE 3, respectively. A cut-off VEGF level of 310 ng/mL predicted the presence of psoriasis with a sensitivity of 50% and specificity of 77%. The results of this pioneering study indicate that SCUBE protein family appears to have a probable role in the pathogenesis and angiogenesis development in psoriasis and SCUBE 1 and 3 may be novel markers of angiogenesis in psoriasis.
Similar content being viewed by others
References
Boehncke WH, Schon MP (2015) Psoriasis. Lancet 386(9997):983–994
Campanati A, Goteri G, Simonetti O, Ganzetti G, Giuliodori K, Giuliano A (2009) Angiogenesis in psoriatic skin and its modifications after administration of etanercept: videocapillaroscopic, histological and immunohistochemical evaluation. Int J Immunopathol Pharmacol 22:371–377
Chandra A, Ray A, Senapati S, Chatterjee R (2015) Genetic and epigenetic basis of psoriasis pathogenesis. Mol Immunol 64:313–323
Detmar M, Brown LF, Claffey KP, Yeo KT, Kocher O, Jackman RW, Berse B, Dvorak HF (1994) Overexpression of vascular permeability factor/vascular endothelial growth factor and its receptors in psoriasis. J Exp Med 180:1141–1146
Fernandez A (2015) Dermatology update: the dawn of targeted treatment. Cleve Clin J Med 82:309–320
Folkman J (1972) Angiogenesis in psoriasis: therapeutic implications. J Invest Dermatol 59:40–43
Goel S, Wong AH, Jain RK (2012) Vascular normalization as a therapeutic strategy for malignant and nonmalignant disease. Cold Spring Harb Perspect Med 2: a006486.
Gudjonsson JE, Johnston A, Sigmundsdottir H, Valdimarsson H (2004) Immunopathogenic mechanisms in psoriasis. Clin Exp Immunol 135:1–8
Heidenreich R, Rocken M, Ghoreschi K (2009) Angiogenesis drives psoriasis pathogenesis. Int J Exp Pathol 90:232–248
Lin YC, Chen CC, Cheng CJ, Yang RB (2011) Domain and functional analysis of a novel breast tumor suppressor protein, SCUBE2. J Biol Chem 286:39–47
Lin YC, Roffler SR, Yan YT, Yang RB (2015) Disruption of Scube2 impairs endochondral bone formation. J Bone Miner Res 30:1255–1267
Lin YC, Lee YC, Li LH, Cheng CJ, Yang RB (2014) Tumor suppressor SCUBE2 inhibits breast-cancer cell migration and invasion through the reversal of epithelial-mesenchymal transition. J Cell Sci 127:85–100
Li W, Man XY, Chen JQ, Zhou J, Cai SQ, Zheng M (2014) Targeting VEGF/VEGFR in the treatment of psoriasis. Discov Med 18:97–104
Mezentsev A, Nikolaev A, Bruskin S (2014) Matrix metalloproteinases and their role in psoriasis. Gene 540:1–10
Mentese A, Fidan E, Sumer AU, Karahan SC, Sonmez M, Altay DU (2012) Is SCUBE 1 a new biomarker for gastric cancer? Cancer Biomark 11:191–195
Nofal A, Al-Makhzangy I, Attwa E, Nassar A, Abdalmoati A (2009) Vascular endothelial growth factor in psoriasis: an indicator of disease severity and control. J Eur Acad Dermatol Venereol 23:803–806
Parisi R, Symmons DP, Griffiths CE, Ashcroft DM (2013) Identification and management of psoriasis and associated comorbidity project team. Global epidemiology of psoriasis: a systematic review of incidence and prevalence. J Invest Dermatol 133:377–385
Schonthaler HB, Huggenberger R, Wculek SK, Detmar M, Wagner EF (2009) Systemic anti-VEGF treatment strongly reduces skin inflammation in a mouse model of psoriasis. Proc Natl Acad Sci USA 106:21264–21269
Tu CF, Tsao KC, Lee SJ, Yang RB (2014) SCUBE3 (signal peptide-CUB-EGF domain-containing protein 3) modulates fibroblast growth factor signaling during fast muscle development. J Biol Chem 289:28–42
Varricchi G, Granata F, Loffredo S, Genovese A, Marone G (2015) Angiogenesis and lymphangiogenesis in inflammatory skin disorders. J Am Acad Dermatol 73:144–153
Wu YY, Peck K, Chang YL et al (2011) SCUBE3 is an endogenous TGF-beta receptor ligand and regulates the epithelial mesenchymal transition in lung cancer. Oncogene 30:682–693
Yanga M, Mingyang G, Yonghe H Jiang Y (2013) Scube regulates synovial angiogenesis-related signaling. Med Hypotheses 81:948–953
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflicts of interest
None.
Ethical approval
The study protocol was approved by Kanuni Sultan Suleyman Research and Training Hospital Ethics Committee on Research.
Rights and permissions
About this article
Cite this article
Capkin, A.A., Demir, S., Mentese, A. et al. Can signal peptide-CUB-EGF domain-containing protein (SCUBE) levels be a marker of angiogenesis in patients with psoriasis?. Arch Dermatol Res 309, 203–207 (2017). https://doi.org/10.1007/s00403-017-1722-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00403-017-1722-7