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Genetic and protein expression of CXCR4 and CD26 and its relation to cell indifferentiation and responsiveness to treatment of colon and rectum neoplasms
Author(s) -
Assis Jéssica Vieira,
Coutinho Lucélia Antunes,
Moraes Vanessa Silva,
Silva Istéfani Dayse,
Grenfell Rafaella Fortini
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.811.12
Subject(s) - cxcr4 , colorectal cancer , rectum , monoclonal antibody , gene expression , chemotherapy , biology , gene , cancer research , cancer , medicine , oncology , antibody , immunology , chemokine , immune system , genetics
The molecular heterogeneity of colorectal cancer (CRC) combined with a lack of methodological standard, which evaluates the effectiveness of the chemotherapeutic treatment, has demonstrated a challenge in the control of the disease, making it necessary to evaluate the gene expression profile of the tumor in an individualized way. Studies have shown that overexpression of the CXCR4 gene combined with the low expression of CD26 has shown a satisfactory prognostic profile and treatment responsiveness. However, the inverse encodes a lower chance of progression‐free survival and evolution in disease staging. Furthermore, studies show that the CXCR4+/CD26−, CXCR4−/CD26+, CXCR4+/CD26+ and CXCR4−/CD26− gene profiles require different antineoplastic treatment protocols to ensure a greater chance of cure. Thus, the analysis of the expression profile of the cited markers may be useful in determining the efficacy of conventional treatments making the approach more assertive. Thus, the objective of this study is to evaluate the gene and protein expression profile of the CXCR4 and CD26 genes in colon and rectum cancer, correlating them to the responsiveness of patients affected by the pathology to chemotherapy through clinical data and their cellular differentiation profile, through the evaluation of epithelial‐mesenchymal transition markers (EMT) and cancer steem cells (CSC). For such analyzes, the CXCR4r protein and peptide portions of CD26r were produced, in which the ELISA assay demonstrates the sensitization of the animals by CXCR4r and CD26r. The next step consists of the production of the anti‐CXCR4r and anti‐CD26r monoclonal antibodies (mAbs) and are being performed according to the protocol adopted by the Antibody Production Platform of Fiocruz/Minas. In parallel, quantitative PCR reactions were performed for CXCR4, CD26, E‐cadherin, vimentin, Oct/3/4 and Sox2, in order to evaluate their gene expression. The predominance of CXCR4‐/CD26+ cells (1:2) was observed and the gene expression of EMT and CSC markers was high in such cell population. To evaluate the protein expression profiles of the CXCR4 and CD26 genes, human samples, positive and negative for CCR, were processed, histopathologically analyzed and submitted to immunohistochemical analysis. Such analysis showed a more undifferentiated profile when we observed the pattern of CXCR4‐/CD26+ gene expression. As perspectives, the results obtained in the analyzes of gene expression will be correlated to the clinical data and we will proceed to the finalization of the production of mAbs anti‐CXCR4 and CD26, which will serve as a subsidy to evaluate the effectiveness of the proposed treatments. Finally, it is expected that the variation in the expression profiles of the CXCR4 and CD26 genes actually encode significant differences in the prognosis of the CRC, besides helping in the medical decision making regarding effective chemotherapeutic strategies. Financial support: Fiocruz, CNPq, FIOCÂNCER IRR. Support or Funding Information Financial support: Fiocruz, CNPq, FIOCÂNCER IRR. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .