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) for MMP1, and (ii) determination of MMP1 and MMP3 concentrations 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.
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) for MMP1, and (ii) determination of MMP1 and MMP3 concentrations 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.
Authors: Jacques Ferlay; Hai-Rim Shin; Freddie Bray; David Forman; Colin Mathers; Donald Maxwell Parkin Journal: Int J Cancer Date: 2010-12-15 Impact factor: 7.396
Authors: S Kurahara; M Shinohara; T Ikebe; S Nakamura; M Beppu; A Hiraki; H Takeuchi; K Shirasuna Journal: Head Neck Date: 1999-10 Impact factor: 3.147
Authors: J L Rutter; T I Mitchell; G Butticè; J Meyers; J F Gusella; L J Ozelius; C E Brinckerhoff Journal: Cancer Res Date: 1998-12-01 Impact factor: 12.701
Authors: Karolina Elżbieta Kaczor-Urbanowicz; Carmen Martin Carreras-Presas; Katri Aro; Michael Tu; Franklin Garcia-Godoy; David Tw Wong Journal: Exp Biol Med (Maywood) Date: 2016-12-08
Authors: Oneida A Arosarena; Eric W Barr; Ryan Thorpe; Hilary Yankey; Joseph T Tarr; Fayez F Safadi Journal: J Cell Physiol Date: 2017-04-25 Impact factor: 6.384
Authors: Dina V Hingorani; Aaron J Lemieux; Joseph R Acevedo; Heather L Glasgow; Suraj Kedarisetty; Michael A Whitney; Alfredo A Molinolo; Roger Y Tsien; Quyen T Nguyen Journal: Oral Oncol Date: 2017-06-27 Impact factor: 5.337
Authors: Yunxia Wan; Xi Zhang; Kai Dun Tang; Tony Blick; Liz Kenny; Erik W Thompson; Chamindie Punyadeera Journal: Mol Biol Rep Date: 2021-05-21 Impact factor: 2.316