Low expression of RECK in oral squamous cell carcinoma patients induces a shorter survival rate through an imbalance of RECK/MMPs.

BACKGROUND

RECK, as a negative MMP regulator, is extensively expressed in normal cells but decreased in tumors. In OSCC, the relationship between RECK and MMPs and the potential prognostic impact remains unclear. In this research, for the first time, we investigated the expression of RECK associated with MMPs during OSCC carcinogenesis in a large sample and its association with 5-year survival rate.

MATERIAL AND METHODS

Immunohistochemical SP technique was applied to study the expression of RECK and MMP-2 and MMP-9 in 108 cases of OSCC and 30 normal oral mucosae. Univariate and multivariate Cox regression analysis was utilized for disease-free survival and overall survival, and analyzed by Kaplan-Meier method regarding RECK expression in patients of OSCC.

RESULTS

We found lower expression of RECK in OSCC was 51.85% (56/108) compared with 93.33% (28/30) in the control group. However, the higher expression of MMP-2 and MMP-9 was 74.07% (80/108) and 70.37% (76/108) in OSCC, respectively, compared with 20% (6/30) and 13.3% (4/30) in the control group. Furthermore, the decrease of RECK expression and the increase of MMP-2, and -9 expression were significantly correlated with the loss of histologic differentiation, the occurrence of lymphatic metastasis, and the increase of OSCC clinical stage (<0.05). OSCC patients with a low level of RECK expression had a lower rate of 5-year survival.

CONCLUSION

RECK may prevent metastasis and improve OSCC patients' prognosis through a RECK/MMP-2, and -9 imbalance. Furthermore, RECK is a prospective prognostic indicator and therapeutic target for cancer molecular targeting therapy. Low expression of RECK may be a significant negative prognostic predictor.