DOI: https://doi.org/None

N.I. Pospekhova (1), V.P. Shubin (1), A.S. Tsukanov 1), V.N. Kashnikov (1), S.A. Frolov 1), S.I. Achkasov (1), O.I. Sushkov (1), Yu.A. Shelygin (1,2) 1 -State Scientific Center of Coloproctology, Salyama Adilya Str., 2, Moscow, Russian Federation, 123423 2 -Department of Coloproctology, Russian Medical Academy of Postgraduate Education, Salyama Adilya Str., 2, Moscow, Russian Federation, 123423

Introduction. Colorectal cancer (CRC) often metastasizes even if the tumor is small in size that is the main cause of death. Complex process of epithelial-mesenchymal transition (EMT) is required for dissemination of tumor cells. EMT leads to the transformation of epithelial phenotype of cells to their mesenchymal phenotype. The aim of the study was the determination of epithelial-mesenchymal transition based on the gene expression profile and somatic molecular genetic alterations in colon cancer samples at different stages, including the peritoneal carcinomatosis. Methods. Forty six CRC patients including cases with peritoneal carcinomatosis were investigated. To determine the program for EMT ZEB1, ZEB2, CDH1, VIM, SNAIL1 gene expression profiling was analyzed with the use of real-time PCR. Somatic mutations in KRAS and BRAF were analyzed by direct sequences. Microsatellite instability was determined by the fragment analysis. Results. Epithelial-mesenchymal transition was detected in 16 cases (34,8%), including 10 of 11 patients with peritoneal carcinomatosis. These mesenchymal subtype tumors were distinguished with high frequency of somatic mutations, microsatellite stability and low grade of differentiation Conclusion. Identification of EMT can provide an indication of high metastatic potential of the tumor that is especially important at the early stages of the disease.
colon cancer, gene expression profile, epithelial-mesenchymal transition, peritoneal carcinomatosis

Список литературы: 
  1. Thiery J.P. Epithelial-mesenchymal transitions in tumour progression. Nat. Rev. Cancer. 2002; 6: 442–54.
  2. Yang J., Weinberg R.A. Epithelial-mesenchymal transition: at the crossroads of development and tumor metastasis. Dev. Cell. 2008; 14 (6): 818–29.
  3. Thiery J., Acloque H., Huang R., Nieto M. Epithelial-Mesenchymal Transitions in Development and Disease. Cell. 2009; 139: 871–90.
  4. Roepman P., Schlicker A., Tabernero J. et al. Colorectal cancer intrinsic subtypes predict chemotherapy benefit, deficient mismatch repair and epithelial-to-mesenchymal transition. Int. J. Cancer. 2013; 134 (3): 552–62.
  5. Marisa L., de Reynies A., Duval A. et al. Gene Expression Classification of Colon Cancer into Molecular Subtypes: Characterization, Validation, and Prognostic Value. PLoS Med. 2013; 10 (5): e1001453.
  6. Zhu J., Wang J., Shi Z. et al. Deciphering Genomic Alterations in Colorectal Cancer through Transcriptional Subtype-Based Network Analysis. PLoS One. 2013; 8 (11): e79282.
  7. Peinado H., Olmeda D., Cano A. Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nature Rev. Cancer. 2007; 7: 415–28.
  8. Joyce T., Cantarella D., Isella C. et al. A molecular signature for Epithelial to Mesenchymal transition in a human colon cancer cell system is revealed by large-scale microarray analysis. Clin. Exp. Metastasis. 2009; 26 (6): 569–87.
  9. Lim J., Thiery J. Epithelial-mesenchymal transitions: insights from Development. Development. 2012; 139: 3471–86.
  10. Sipos F., Galamb O. Epithelial-to-mesenchymal and mesenchymal-to-epithelial transitions in the colon. World J. Gastroenterol. 2012; 18 (7): 601–8.
  11. Souglakos J., Philips J., Wang R. et al. Prognostic and predictive value of common mutations for treatment response and survival in patients with metastatic colorectal cancer. Br. J. Cancer. 2009; 101 (3): 465–72.
  12. Makrodouli E., Oikonomou E., Koc M. et al. BRAF and RAS oncogenes regulate Rho GTPase pathways to mediate migration and invasion properties in human colon cancer cells: a comparative study. Mol. Cancer. 2011; 10: 118.