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

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 (r_s =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.