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. 2017 Oct 24:10:5099-5105.
doi: 10.2147/OTT.S149231. eCollection 2017.

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

Eik Schiegnitz  1 , Peer W Kämmerer  2 , Holger Schön  1 , Christoph Gülle  1 , Manfred Berres  3   4 , Keyvan Sagheb  1 , Bilal Al-Nawas  5
Affiliations

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

Eik Schiegnitz et al. Onco Targets Ther. .

Abstract

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: IGF; MMP; OSCC; oral cancer; oral premalignant lesion; prognosis; serum biomarker.

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Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Survival rate of OSCC patients with IGF-1 serum values ≥ 130 ng/mL (circles, n=41) and with IGF-1 serum values <130 ng/mL (squares, n=40; p=0.043). Abbreviations: IGF, insulin-like growth factor; OSCC, oral squamous cell carcinoma.
Figure 2
Figure 2
Survival rate of OSCC patients with IGFBP-3 serum values ≥ 3.1 μg/mL (circles, n=42) and with IGFBP-3 serum values <3.1 μg/mL (squares, n=39; p=0.149). Abbreviations: IGF, insulin-like growth factor; IGFBP, IGF-binding protein; OSCC, oral squamous cell carcinoma.
Figure 3
Figure 3
Survival rate of OSCC patients with IGF-1 (≥ 130 ng/mL) and IGFBP-3 (≥ 3.1 μg/mL) serum values (circles, n=51) and with IGF-1 (<130 ng/mL) and IGFBP-3 (<3.1 μg/mL) serum values (squares, n=30; p=0.031). Abbreviations: IGF, insulin-like growth factor; IGFBP, IGF-binding protein; OSCC, oral squamous cell carcinoma.
Figure 4
Figure 4
Correlation between serum IGF-1 (pg/mL) and IGFBP-3 (ng/mL) levels. Abbreviations: IGF, insulin-like growth factor; IGFBP, IGF-binding protein.
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