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Expression of Selenoprotein Genes and Association with Selenium Status in Colorectal Adenoma and Colorectal Cancer.

Abstract

Dietary selenium (Se) intake is essential for synthesizing selenoproteins that are important in countering oxidative and inflammatory processes linked to colorectal carcinogenesis. However, there is limited knowledge on the selenoprotein expression in colorectal adenoma (CRA) and colorectal cancer (CRC) patients, or the interaction with Se status levels. We studied the expression of seventeen Se pathway genes (including fifteen of the twenty-five human selenoproteins) in RNA extracted from disease-normal colorectal tissue pairs, in the discovery phase of sixty-two CRA/CRC patients from Ireland and a validation cohort of a hundred and five CRC patients from the Czech Republic. Differences in transcript levels between the disease and paired control mucosa were assessed by the Mann-Whitney U-test. GPX2 and TXNRD3 showed a higher expression and GPX3, SELENOP, SELENOS, and SEPHS2 exhibited a lower expression in the disease tissue from adenomas and both cancer groups (p-values from 0.023 to <0.001). In the Czech cohort, up-regulation of GPX1, SELENOH, and SOD2 and down-regulation of SELENBP1, SELENON, and SELENOK (p-values 0.036 to <0.001) was also observed. We further examined the correlation of gene expression with serum Se status (assessed by Se and selenoprotein P, SELENOP) in the Irish patients. While there were no significant correlations with both Se status markers, SELENOF, SELENOK, and TXNRD1 tumor tissue expression positively correlated with Se, while TXNRD2 and TXNRD3 negatively correlated with SELENOP. In an analysis restricted to the larger Czech CRC patient cohort, Cox regression showed no major association of transcript levels with patient survival, except for an association of higher SELENOF gene expression with both a lower disease-free and overall survival. Several selenoproteins were differentially expressed in the disease tissue compared to the normal tissue of both CRA and CRC patients. Altered selenoprotein expression may serve as a marker of functional Se status and colorectal adenoma to cancer progression.

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  • Authors+Show Affiliations

    ,

    Cancer Biology and Therapeutics Group, UCD Conway Institute, University College Dublin, D04 V1W8 Dublin, Ireland. david.hughes@ucd.ie.

    ,

    Biomedical Centre, Medical and Teaching School Pilsen, Charles University in Prague, 323 00 Pilsen, Czech Republic. terez.kunicka@gmail.com.

    ,

    Institute for Experimental Endocrinology, University Medical School Berlin, D-13353 Berlin, Germany. lutz.schomburg@charite.de.

    ,

    Biomedical Centre, Medical and Teaching School Pilsen, Charles University in Prague, 323 00 Pilsen, Czech Republic. vena.liska@skaut.cz. Teaching Hospital and Medical School, Charles University in Prague, 306 05 Pilsen, Czech Republic. vena.liska@skaut.cz.

    ,

    Department of Pathology and Laboratory Medicine, St. Vincent's University Hospital, D04 T6F4 Dublin, Ireland. n.swan@svuh.ie.

    Biomedical Centre, Medical and Teaching School Pilsen, Charles University in Prague, 323 00 Pilsen, Czech Republic. pavel.soucek@szu.cz. Teaching Hospital and Medical School, Charles University in Prague, 306 05 Pilsen, Czech Republic. pavel.soucek@szu.cz.

    Source

    Nutrients 10:11 2018 Nov 21 pg

    MeSH

    Adenoma
    Aged
    Aged, 80 and over
    Cohort Studies
    Colorectal Neoplasms
    Czech Republic
    Female
    Gene Expression Regulation
    Genetic Markers
    Glutathione Peroxidase
    Humans
    Ireland
    Male
    Middle Aged
    Proportional Hazards Models
    Selenium
    Selenoprotein P
    Selenoproteins
    Thioredoxin Reductase 1
    Thioredoxin-Disulfide Reductase

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    30469315

    Citation

    Hughes, David J., et al. "Expression of Selenoprotein Genes and Association With Selenium Status in Colorectal Adenoma and Colorectal Cancer." Nutrients, vol. 10, no. 11, 2018.
    Hughes DJ, Kunická T, Schomburg L, et al. Expression of Selenoprotein Genes and Association with Selenium Status in Colorectal Adenoma and Colorectal Cancer. Nutrients. 2018;10(11).
    Hughes, D. J., Kunická, T., Schomburg, L., Liška, V., Swan, N., & Souček, P. (2018). Expression of Selenoprotein Genes and Association with Selenium Status in Colorectal Adenoma and Colorectal Cancer. Nutrients, 10(11), doi:10.3390/nu10111812.
    Hughes DJ, et al. Expression of Selenoprotein Genes and Association With Selenium Status in Colorectal Adenoma and Colorectal Cancer. Nutrients. 2018 Nov 21;10(11) PubMed PMID: 30469315.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Expression of Selenoprotein Genes and Association with Selenium Status in Colorectal Adenoma and Colorectal Cancer. AU - Hughes,David J, AU - Kunická,Tereza, AU - Schomburg,Lutz, AU - Liška,Václav, AU - Swan,Niall, AU - Souček,Pavel, Y1 - 2018/11/21/ PY - 2018/09/10/received PY - 2018/11/13/revised PY - 2018/11/14/accepted PY - 2018/11/25/entrez PY - 2018/11/25/pubmed PY - 2019/3/6/medline KW - biomarkers KW - cancer risk KW - colorectal adenoma KW - colorectal cancer KW - colorectal neoplasm KW - gene expression KW - selenium (Se), selenoproteins KW - selenium status KW - selenoprotein P JF - Nutrients JO - Nutrients VL - 10 IS - 11 N2 - Dietary selenium (Se) intake is essential for synthesizing selenoproteins that are important in countering oxidative and inflammatory processes linked to colorectal carcinogenesis. However, there is limited knowledge on the selenoprotein expression in colorectal adenoma (CRA) and colorectal cancer (CRC) patients, or the interaction with Se status levels. We studied the expression of seventeen Se pathway genes (including fifteen of the twenty-five human selenoproteins) in RNA extracted from disease-normal colorectal tissue pairs, in the discovery phase of sixty-two CRA/CRC patients from Ireland and a validation cohort of a hundred and five CRC patients from the Czech Republic. Differences in transcript levels between the disease and paired control mucosa were assessed by the Mann-Whitney U-test. GPX2 and TXNRD3 showed a higher expression and GPX3, SELENOP, SELENOS, and SEPHS2 exhibited a lower expression in the disease tissue from adenomas and both cancer groups (p-values from 0.023 to <0.001). In the Czech cohort, up-regulation of GPX1, SELENOH, and SOD2 and down-regulation of SELENBP1, SELENON, and SELENOK (p-values 0.036 to <0.001) was also observed. We further examined the correlation of gene expression with serum Se status (assessed by Se and selenoprotein P, SELENOP) in the Irish patients. While there were no significant correlations with both Se status markers, SELENOF, SELENOK, and TXNRD1 tumor tissue expression positively correlated with Se, while TXNRD2 and TXNRD3 negatively correlated with SELENOP. In an analysis restricted to the larger Czech CRC patient cohort, Cox regression showed no major association of transcript levels with patient survival, except for an association of higher SELENOF gene expression with both a lower disease-free and overall survival. Several selenoproteins were differentially expressed in the disease tissue compared to the normal tissue of both CRA and CRC patients. Altered selenoprotein expression may serve as a marker of functional Se status and colorectal adenoma to cancer progression. SN - 2072-6643 UR - https://www.unboundmedicine.com/medline/citation/30469315/Expression_of_Selenoprotein_Genes_and_Association_with_Selenium_Status_in_Colorectal_Adenoma_and_Colorectal_Cancer_ L2 - http://www.mdpi.com/resolver?pii=nu10111812 DB - PRIME DP - Unbound Medicine ER -