Open Access

Expression of ERCC1, RRM1, TUBB3 in correlation with apoptosis repressor ARC, DNA mismatch repair proteins and p53 in liver metastasis of colorectal cancer

  • Authors:
    • Csaba Tóth
    • Farkas Sükösd
    • Erzsébet Valicsek
    • Esther Herpel
    • Peter Schirmacher
    • Marcus Renner
    • Christoph Mader
    • László Tiszlavicz
    • Jörg Kriegsmann
  • View Affiliations

  • Published online on: September 14, 2017     https://doi.org/10.3892/ijmm.2017.3136
  • Pages: 1457-1465
  • Copyright: © Tóth et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Liver metastasis in colorectal cancer is common and the primary treatment is chemotherapy. To date, there is no routinely used test in clinical practice to predict the effectiveness of conventional chemotherapy. Therefore, biomarkers with predictive value for conventional chemotherapy would be of considerable benefit in treatment planning. We analysed three proteins [excision repair cross-complementing 1 (ERCC1), ribonucleoside-diphosphate reductase 1 (RRM1) and class III β-tubulin (TUBB3)] in colorectal cancer liver metastasis. We used tissue microarray slides with 101 liver metastasis samples, stained for ERCC1, RRM1 and TUBB3 and established scoring systems (fitted for tissue microarray) for each protein. In statistical analysis, we compared the expression of ERCC1, RRM1 and TUBB3 to mismatch proteins (MLH1, MSH2, MSH6 and PMS2), p53 and to apoptosis repressor protein (ARC). Statistically significant correlations were found between ERCC1, TUBB3 and MLH1, MSH2 and RRM1 and MSH2, MSH6. Noteworthy, our analysis revealed a strong significant correlation between cytoplasmic ARC expression and RRM1, TUBB3 (p=0.000 and p=0.001, respectively), implying an additional role of TUBB3 and RRM1 not only in therapy resistance, but also in the apoptotic machinery. Our data strengthens the importance of ERCC1, TUBB3 and RRM1 in the prediction of chemotherapy effectiveness and suggest new functional connections in DNA repair, microtubule network and apoptotic signaling (i.e. ARC protein). In conclusion, we showed the importance and need of predictive biomarkers in metastasized colorectal cancer and pointed out the relevance not only of single predictive markers but also of their interactions with other known and newly explored relations between different signaling pathways.
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November-2017
Volume 40 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Tóth C, Sükösd F, Valicsek E, Herpel E, Schirmacher P, Renner M, Mader C, Tiszlavicz L and Kriegsmann J: Expression of ERCC1, RRM1, TUBB3 in correlation with apoptosis repressor ARC, DNA mismatch repair proteins and p53 in liver metastasis of colorectal cancer. Int J Mol Med 40: 1457-1465, 2017
APA
Tóth, C., Sükösd, F., Valicsek, E., Herpel, E., Schirmacher, P., Renner, M. ... Kriegsmann, J. (2017). Expression of ERCC1, RRM1, TUBB3 in correlation with apoptosis repressor ARC, DNA mismatch repair proteins and p53 in liver metastasis of colorectal cancer. International Journal of Molecular Medicine, 40, 1457-1465. https://doi.org/10.3892/ijmm.2017.3136
MLA
Tóth, C., Sükösd, F., Valicsek, E., Herpel, E., Schirmacher, P., Renner, M., Mader, C., Tiszlavicz, L., Kriegsmann, J."Expression of ERCC1, RRM1, TUBB3 in correlation with apoptosis repressor ARC, DNA mismatch repair proteins and p53 in liver metastasis of colorectal cancer". International Journal of Molecular Medicine 40.5 (2017): 1457-1465.
Chicago
Tóth, C., Sükösd, F., Valicsek, E., Herpel, E., Schirmacher, P., Renner, M., Mader, C., Tiszlavicz, L., Kriegsmann, J."Expression of ERCC1, RRM1, TUBB3 in correlation with apoptosis repressor ARC, DNA mismatch repair proteins and p53 in liver metastasis of colorectal cancer". International Journal of Molecular Medicine 40, no. 5 (2017): 1457-1465. https://doi.org/10.3892/ijmm.2017.3136