Abstract
Recent evidence suggested an important role of matrix metalloproteinases 16 (MMP16) in the progression of several cancers. However, the contribution of MMP16 to colorectal cancer (CRC) remains elusive. In this study, we combined analyzed the MMP16 expression in The Cancer Genome Atlas (TCGA), GSE39582 database and in-house database. In TCGA and GSE39584 database, the log-rank test demonstrated that overall survival (OS) for patients with low MMP16 expression in tumor tissues was significantly higher than those with high expression (P < 0.05). In the validation cohort, high MMP16 expression was significantly correlated with N stage (P = 0.008) and lymphovascular invasion (P = 0.002). The 5-year OS and disease free survival (DFS) in high and low MMP16 expression groups were 66.0% and 80.6%, 54.3% and 72.8%, respectively. Univariate and multivariate analysis showed that high MMP16 expression was an independently prognosis factor for both OS and DFS (P < 0.05). Functional study found that silencing MMP16 expression could inhibit migration and invasion of colon cancer cells. In conclusion, high expression of MMP16 is associated with the aggressive malignant behavior and poor survival outcome of CRC patients. MMP16 can serve as an indicator of prognosis as well as a potential novel target for treatment of CRC patients.
Highlights
Variable Sex Male Female Age Grade G1 G2 G3 T stage T1/T2 T3/T4 TX N stage N0 N1 N2 Nx M stage M0 M1 Mx Lymphovascular invasion Negative Positive Unknown Perineural invasion Negative Positive
We divided the patients in The Cancer Genome Atlas (TCGA) cohort into low or high risk subgroups according to the optimal cutoff value determined by ROC curve in terms of MMP16 expression levels
Local recurrence and distant metastasis are suggested to be the key reasons for poor prognosis and cancer related death in tumor patients
Summary
Variable Sex Male Female Age Grade G1 G2 G3 T stage T1/T2 T3/T4 TX N stage N0 N1 N2 Nx M stage M0 M1 Mx Lymphovascular invasion Negative Positive Unknown Perineural invasion Negative Positive. Functional studies were conducted to figure out the role of MMP16 in oncogenesis
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