OncoTargets and Therapy (Oct 2017)

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

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

Journal volume & issue
Vol. Volume 10
pp. 5099 – 5105

Abstract

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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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