Expression of the matrix metalloproteases 2, 14, 24, and 25 and tissue inhibitor 3 as potential molecular markers in advanced human gastric cancer.

BACKGROUND:During progression of gastric cancer (GC), degradation of the extracellular matrix is mediated by the matrix metalloproteases (MMPs) and their tissue inhibitors (TIMPs): changes in the expression of these have been related to unfavorable prognosis in GC. OBJECTIVE:To analyze the expression of certain MMPs and TIMPs in chronic superficial gastritis (SG) and GC. METHODS:The expression of MMPs and TIMPs was determined using qRT-PCR; the expression was classified, using threshold cycle (C(T)) values, as very high (C(T) ≤ 25), high (C(T) = 26-30), moderate (C(T) = 31-35), low (C(T) = 36-39), or not detected (C(T) = 40). Strength of association was estimated between the proteins, which were detected by Western blot, and the risk of developing GC. RESULTS:We found a high expression of MMP1, MMP2, MMP14, TIMP1, and TIMP3; moderate one of MMP9 and MMP25, and low one of MMP13 and MMP24 in both tissues. In absolute mRNA levels, significant differences were found in expression of MMP2, MMP24, and MMP25, which are overexpressed in GC compared with SG. The presence of the proteins MMP-14 and TIMP-3 was associated with the risk of developing GC. CONCLUSIONS:We consider that MMP2, MMP24, and MMP25 and the proteins MMP-14 and TIMP-3 could be candidates for prognostic molecular markers in GC.

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