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. <i>GPX2</i> and <i>TXNRD3</i> showed a higher expression and <i>GPX3</i>, <i>SELENOP</i>, <i>SELENOS</i>, and <i>SEPHS2</i> exhibited a lower expression in the disease tissue from adenomas and both cancer groups (<i>p</i>-values from 0.023 to <0.001). In the Czech cohort, up-regulation of <i>GPX1</i>, <i>SELENOH</i>, and <i>SOD2</i> and down-regulation of <i>SELENBP1</i>, <i>SELENON</i>, and <i>SELENOK</i> (<i>p</i>-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, <i>SELENOF</i>, <i>SELENOK</i>, and <i>TXNRD1</i> tumor tissue expression positively correlated with Se, while <i>TXNRD2</i> and <i>TXNRD3</i> negatively correlated with <i>SELENOP</i>. 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 <i>SELENOF</i> 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.