Two-dimensional gel electrophoresis analysis of the leiomyoma interstitial fluid reveals altered protein expression with a possible involvement in pathogenesis.
Uterine leiomyoma is the most common smooth benign neoplasm. In the present study, we analyzed the global interstitial fluid (IF) profile of leiomyoma vs. normal myometrium to identify protein dysregulation involved in leiomyoma pathogenesis. Two-dimensional gel electrophoresis and mass spectrometry were used to generate and compare the global interstitial fluid profiles of the leiomyoma and of the normal tissue. Two proteins were validated by immunohistochemistry. By comparing the interstitial fluid profile of the leiomyoma with that of the normal myometrium, the levels of seven proteins were found to be significantly different: four structural organization proteins (desmin, prelamin-A/C, transgelin and α-actinin-1), an inflammatory response (α1-antitrypsin), a response to oxidative stress (peroxiredoxin-2), and a folding protein (heat shock 70 kDa protein 1A/1B). Desmin, α1-antitrypsin and peroxiredoxin-2 were upregulated in the leiomyoma, whereas heat shock 70 kDa protein 1A/1B, α-actinin-1, prelamin-A/C and transgelin were downregulated. Desmin and α1-antitrypsin were further validated by immunohistochemistry. By identifying proteins with altered expression levels compared to the myometrium from several pathways of the leiomyoma pathogenesis, we found the leiomyoma interstitial fluid to have a characteristic proteomic profile. A better appreciation of the pathophysiology of the disease can be useful in the development of conservative treatments that serve as viable alternatives to hysterectomy.
Institute for Maternal and Child Health - IRCCS 'Burlo Garofolo', Trieste, Italy.
Blendi
B
Ura
Institute for Maternal and Child Health - IRCCS 'Burlo Garofolo', Trieste, Italy.
Federica
F
Scrimin
Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
Fabrizio
F
Zanconati
Department of Biomedical Sciences, University of Padua, Padua, Italy.
Giorgio
G
Arrigoni
Institute for Maternal and Child Health - IRCCS 'Burlo Garofolo', Trieste, Italy.
Lorenzo
L
Monasta
UCO Pathological Anatomy and Histology, Azienda Ospedaliera-Universitaria Ospedali Riuniti, Trieste, Italy.
Andrea
A
Romano
Institute for Maternal and Child Health - IRCCS 'Burlo Garofolo', Trieste, Italy.
Rubina
R
Banco
Department of Medical, Surgery and Health Sciences, University of Trieste, Trieste, Italy.
Marina
M
Zweyer
Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy.
Daniela
D
Milani
Institute for Maternal and Child Health - IRCCS 'Burlo Garofolo', Trieste, Italy.
Giuseppe
G
Ricci
D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis*; D015180:Electrophoresis, Gel, Two-Dimensional; D045604:Extracellular Fluid / Q000737:chemistry*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007889:Leiomyoma / Q000235:genetics*; D013058:Mass Spectrometry; D008875:Middle Aged; D009215:Myometrium / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D059467:Transcriptome; D014594:Uterine Neoplasms / Q000235:genetics*
D014408:Biomarkers, Tumor