Tumor and salivary matrix metalloproteinase levels are strong diagnostic markers of oral squamous cell carcinoma

Abstract

Background: The matrix metalloproteinases (MMP) cause degradation of the extracellular matrix and basement membranes, and thus may play a key role in cancer development. Methods: In our search for biomarkers for oral squamous cell carcinomas (OSCC), we compared primary OSCC, oral dysplasia and control subjects with respect to: (i) expression of MMP1, MMP3, MMP10, and MMP12 in oral epithelial tissue using Affymetrix U133 2.0 Plus GeneChip arrays, followed by quantitative reverse transcription-PCR (qRT-PCR) forMMP1, and (ii) determination ofMMP1andMMP3concentrations in saliva. Results: MMP1 expression in primary OSCC (n = 119) was >200-fold higher (P = 7.16 × 10 -40) compared with expression levels in nonneoplastic oral epithelium from controls (n = 35). qRT-PCR results on 30 cases and 22 controls confirmed this substantial differential expression. The exceptional discriminatory power to separate OSCC from controls was validated in two independent testing sets (AUC% = 100; 95% CI: 100-100 and AUC% = 98.4; 95% CI: 95.6-100). Salivary concentrations of MMP1 and MMP3 in OSCC patients (33 stage I/II, 26 stage III/IV) were 6.2 times (95% CI: 3.32-11.73) and 14.8 times (95% CI: 6.75-32.56) higher, respectively, than in controls, and displayed an increasing trend with higher stage disease. Conclusion: Tumor and salivary MMPs are robust diagnostic biomarkers of OSCC. Impact: The capacity of MMP gene expression to identify OSCC provides support for further investigation into MMPs as potential markers for OSCC development. Detection of MMP proteins in saliva in particular may provide a promising means to detect and monitor OSCC noninvasively. ©2011 AACR.