Hemorrhoids and matrix metalloproteinases: A multicenter study on the predictive role of biomarkers.
BACKGROUND
An association between hemorrhoidal disease and matrix metalloproteinases (MMPs) has been described previously. MMPs regulate extracellular structural proteins and tissue remodeling. Neutrophil gelatinase-associated lipocalin (NGAL) is involved in the regulation of MMP activity. The aim of this work was to study the relationship between tissue immunoreactive levels of MMPs and NGAL and different stages of hemorrhoids.


METHODS
In a multicenter, open-label, prospective study, the population under investigation consisted of 2 groups: group I (with symptomatic hemorrhoids; Goligher grade I-IV) and group II (healthy volunteers).


RESULTS
We enrolled 97 patients with hemorrhoids: 21 with grade I hemorrhoids, 37 with grade II, 14 with grade III, and 25 with grade IV. Finally, 90 healthy volunteers (53 males and 37 females; age range, 19-70 years; median, 56) were enrolled in group II. Enzyme-linked immunosorbent assay and Western blot analysis revealed greater levels of immunoreactive MMPs and NGAL in all patients with hemorrhoids. We recorded significantly greater levels of MMP-1 and MMP-3 in grade I and II patients compared with control, and greater levels of MMP-3, MMP-7, MMP-8, and MMP-9 in grade III compared with grade II. MMP-9 and NGAL were particularly increased in patients with grade IV especially in case of thrombosed hemorrhoids.


CONCLUSIONS
These results provide potentially important insights into the understanding of the natural history of hemorrhoids. MMPs and NGAL play a role in development of disease and may represent molecular markers for the complications such as hemorrhoidal thrombosis.
Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, University Magna Graecia of Catanzaro, Catanzaro, Italy; Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy. Electronic address: rserra@unicz.it.
Raffaele
R
Serra
Department of Health Sciences, University of Catanzaro, Catanzaro, Italy.
Luca
L
Gallelli
Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy.
Raffaele
R
Grande
Department of Clinical Medicine and Surgery, University of Naples "Federico II," Naples, Italy.
Bruno
B
Amato
Department of Dentistry and Medical and Surgical Experimental Sciences, University of Messina, Messina, Italy.
Giovanni
G
De Caridi
Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy.
Giuseppe
G
Sammarco
Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy.
Francesco
F
Ferrari
Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy.
Lucia
L
Butrico
Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy.
Gaetano
G
Gallo
Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy.
Antonia
A
Rizzuto
Interuniversity Center of Phlebolymphology (CIFL), International Research and Educational Program in Clinical and Experimental Biotechnology, University Magna Graecia of Catanzaro, Catanzaro, Italy; Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy.
Stefano
S
de Franciscis
Department of Medical and Surgical Sciences, University of Catanzaro, Catanzaro, Italy.
Rosario
R
Sacco
D000209:Acute-Phase Proteins / Q000378:metabolism; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D016022:Case-Control Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D064368:Healthy Volunteers; D006484:Hemorrhoids / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D000071068:Lipocalin-2; D054834:Lipocalins / Q000378:metabolism; D008297:Male; D053505:Matrix Metalloproteinases, Secreted / Q000378:metabolism*; D008875:Middle Aged; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000378:metabolism
D000209:Acute-Phase Proteins; D015415:Biomarkers; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D053505:Matrix Metalloproteinases, Secreted