Involvement Of Matrix Metallo Proteinase-14in Colorectal Carcinoma

Objective:To study the gene and protein expressions of matrix metalloproteinase-14(MMP-14) in human colorectal carcinoma and investigate the clinical significances.Methods:(1) The expressions of MMP-14gene in24freshly frozen specimens of colorectalcarcinoma and their adjacent normal tissues were detected by real-time quantitativePCR (RQ-PCR);(2) The expression of MMP-14was detected by western blot in8fresh humancolorectal carcinoma and tumor-adjacent tissues; the expression of MMP-14were alsodetected by immunohistochemistry in90paraffin-embedded cancer specimens fromoperated patients with colorectal carcinoma and30tumor-adjacent tissues, therelationship between the expression of MMP-14and colorectal carcinoma’sclinicopathological parameters were analyzed;(3) The survival time of the post-operation patients were followed up.Kaplan-Meier method, logrank univariate and Cox proportional hazards regressionmodel were used to analyze the relationship between MMP-14expression and prognosisof the cases with colorectal carcinoma.Result:(1) RQ-PCR results showed that the expressions of MMP-14gene were higher incolorectal carcinoma [1.4385(0.0048-7.3106)] than those in the adjacent tissues[0.1035(0.0012-5.1337)], the difference was statistically significant (P=0.0088).Agarose gel electrophoresis showed that the PCR product size of MMP-14wasconsistent with designed size. The expression intensity of MMP-14was correlated withinvasive depth (P=0.04) and Dukes classification (P=0.03) in colorectal carcinoma. Theexpression intensity of MMP-14was not correlated with age (P=0.95), gender (P=0.10)and histolo4gical grade (P=0.62) in colorectal carcinoma; (2) Immunohistochemistry and western blot analysis showed that MMP-14expression in tumor tissues were higher than that in adjacent non-tumorous tissues. Theexpression intensity of MMP-14protein was correlated with lymph node metastasis(P=0.042), invasive depth (P=0.021) and Dukes classification (P=0.018) in colorectalcarcinoma;(3) Kaplan-Meier survival curves showed that high MMP-14expression correlatedto short survival time. Univariate analysis showed that parameters of the tumorhistological grade, with or without lymph node metastasis, invasive depth, Dukesclassification and MMP-14expression are correlated with survival time of thepost-operation patients (P<0.05). Cox proportional hazards model showed that MMP-14was independent prognostic indicators of overall survival.Conclusions:(1) The expression of MMP-14was higher in colorectal carcinoma than in theadjacent non-cancerous tissues;(2) The expression level of MMP-14was correlated with lymph node metastasis,invasive depth, Dukes classification in colorectal carcinoma, and MMP-14was anindependent prognostic indicators of overall survival.