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The matrix metalloproteinase and insulin-like growth factor system in oral cancer – a prospective clinical study

Authors Schiegnitz E, Kämmerer PW, Schön H, Gülle C, Berres M, Sagheb K, Al-Nawas B

Received 15 August 2017

Accepted for publication 22 September 2017

Published 24 October 2017 Volume 2017:10 Pages 5099—5105

DOI https://doi.org/10.2147/OTT.S149231

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Amy Norman

Peer reviewer comments 3

Editor who approved publication: Dr Samir Farghaly

Eik Schiegnitz,1 Peer W Kämmerer,2 Holger Schön,1 Christoph Gülle,1 Manfred Berres,3,4 Keyvan Sagheb,1 Bilal Al-Nawas5

1Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Center, Johannes Gutenberg University of Mainz, Mainz, 2Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Centre Rostock, Rostock, 3Department of Mathematics and Technology, University of Applied Sciences Koblenz, Remagen, 4Institute of Medical Biometry, Epidemiology and Informatics, Johannes Gutenberg University of Mainz, Mainz, 5Department of Oral and Maxillofacial Surgery, Plastic Surgery, University Medical Centre, Martin-Luther University Halle, Halle, Germany

Aim: The absence of reliable single serum biomarkers for oral premalignant lesion (OPL) and oral squamous cell carcinoma (OSCC) limits early diagnosis, monitoring of advanced disease, and prediction of prognosis.
Methods: In this prospective study, serum levels of matrix metalloproteinase (MMP)-2, MMP-3, MMP-13, insulin-like growth factor (IGF)-1, and IGF-binding protein (IGFBP)-3 were measured in 81 untreated OSCC patients, 49 healthy subjects, and 75 individuals with OPLs, and correlated with clinicopathological parameters.
Results: Serum levels of MMP-3 were significantly higher in OSCC patients compared to healthy subjects (p=0.004). Mean IGF-1 and IGFBP-3 levels in OSCC patients were significantly lower in healthy subjects (p=0.001 and p<0.001). OSCC patients with an IGF-1 serum value <130 ng/mL (median) showed a significantly lower survival rate compared to ≥130 ng/mL (p=0.049). Combined use of IGF-1 (<130 ng/mL) and IGFBP-3 (<3.1 µg/mL) resulted in a significantly lower 12-month cumulative survival compared to the complementary set (78.5% vs 93.8%; p=0.031). There was a significantly positive correlation between IGF-1 and IGFBP-3 serum values (rs =0.625, p<0.001).
Conclusion: This study shows that IGF-1 and IGFBP-3 have a vital role in the pathogenesis of OSCC and indicates for the first time that IGF-1 and IGFBP-3 in combination may be applied as potential tools for prognosis of OSCC.

Keywords: oral cancer, OSCC, oral premalignant lesion, serum biomarker, prognosis, IGF, MMP

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