Expression of the Matrix Metalloproteases 2, 14, 24, and 25 and Tissue Inhibitor 3 as Potential Molecular Markers in Advanced Human Gastric Cancer

  • Sol de la Peña
    Biomedical Sciences Doctoral Program, Biomedical Research Center, University of Veracruz, 91190 Xalapa, Veracruz, Mexico
  • Clara Luz Sampieri
    Institute of Public Health, University of Veracruz, 91190 Xalapa, Veracruz, Mexico
  • Mariana Ochoa-Lara
    Public Health Master Program, University of Veracruz, 91190 Xalapa, Veracruz, Mexico
  • Kenneth León-Córdoba
    Dr. Miguel Dorantes Mesa Hospital, 91130 Xalapa, Veracruz, Mexico
  • José María Remes-Troche
    Medical-Biological Research Institute, University of Veracruz, 91700 Veracruz, Veracruz, Mexico

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<jats:p><jats:italic>Background</jats:italic>. 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.<jats:italic>Objective</jats:italic>. To analyze the expression of certain MMPs and TIMPs in chronic superficial gastritis (SG) and GC.<jats:italic>Methods</jats:italic>. The expression of MMPs and TIMPs was determined using qRT-PCR; the expression was classified, using threshold cycle (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:msub><mml:mrow><mml:mi>C</mml:mi></mml:mrow><mml:mrow><mml:mi>T</mml:mi></mml:mrow></mml:msub></mml:mrow></mml:math>) values, as very high (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:msub><mml:mrow><mml:mi>C</mml:mi></mml:mrow><mml:mrow><mml:mi>T</mml:mi></mml:mrow></mml:msub><mml:mo>≤</mml:mo><mml:mn>25</mml:mn></mml:math>), high (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:msub><mml:mrow><mml:mi>C</mml:mi></mml:mrow><mml:mrow><mml:mi>T</mml:mi></mml:mrow></mml:msub><mml:mo>=</mml:mo><mml:mn>26</mml:mn><mml:mtext>–</mml:mtext><mml:mn>30</mml:mn></mml:math>), moderate (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:msub><mml:mrow><mml:mi>C</mml:mi></mml:mrow><mml:mrow><mml:mi>T</mml:mi></mml:mrow></mml:msub><mml:mo>=</mml:mo><mml:mn>31</mml:mn><mml:mtext>–</mml:mtext><mml:mn>35</mml:mn></mml:math>), low (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:msub><mml:mrow><mml:mi>C</mml:mi></mml:mrow><mml:mrow><mml:mi>T</mml:mi></mml:mrow></mml:msub><mml:mo>=</mml:mo><mml:mn>36</mml:mn><mml:mtext>–</mml:mtext><mml:mn>39</mml:mn></mml:math>), or not detected (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:msub><mml:mrow><mml:mi>C</mml:mi></mml:mrow><mml:mrow><mml:mi>T</mml:mi></mml:mrow></mml:msub><mml:mo>=</mml:mo><mml:mn>40</mml:mn></mml:math>). Strength of association was estimated between the proteins, which were detected by Western blot, and the risk of developing GC.<jats:italic>Results</jats:italic>. We found a high expression of<jats:italic>MMP1</jats:italic>,<jats:italic>MMP2</jats:italic>,<jats:italic>MMP14</jats:italic>,<jats:italic>TIMP1,</jats:italic>and<jats:italic>TIMP3</jats:italic>; moderate one of<jats:italic>MMP9</jats:italic>and<jats:italic>MMP25,</jats:italic>and low one of<jats:italic>MMP13</jats:italic>and<jats:italic>MMP24</jats:italic>in both tissues. In absolute mRNA levels, significant differences were found in expression of<jats:italic>MMP2</jats:italic>,<jats:italic>MMP24,</jats:italic>and<jats:italic>MMP25</jats:italic>, 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.<jats:italic>Conclusions</jats:italic>. We consider that<jats:italic>MMP2</jats:italic>,<jats:italic>MMP24,</jats:italic>and<jats:italic>MMP25</jats:italic>and the proteins MMP-14 and TIMP-3 could be candidates for prognostic molecular markers in GC.</jats:p>

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