Integrated Analysis to Study the Relationship between Tumor-Associated Selenoproteins: Focus on Prostate Cancer

Abstract

Selenoproteins are proteins that contain selenium within selenocysteine residues. To date, twenty-five mammalian selenoproteins have been identified; however, the functions of nearly half of these selenoproteins are unknown. Although alterations in selenoprotein expression and function have been suggested to play a role in cancer development and progression, few detailed studies have been carried out in this field. Network analyses and data mining of publicly available datasets on gene expression levels in different cancers, and the correlations with patient outcome, represent important tools to study the correlation between selenoproteins and other proteins present in the human interactome, and to determine whether altered selenoprotein expression is cancer type-specific, and/or correlated with cancer patient prognosis. Therefore, in the present study, we used bioinformatics approaches to (i) build up the network of interactions between twenty-five selenoproteins and identify the most inter-correlated proteins/genes, which are named HUB nodes; and (ii) analyze the correlation between selenoprotein gene expression and patient outcome in ten solid tumors. Then, considering the need to confirm by experimental approaches the correlations suggested by the bioinformatics analyses, we decided to evaluate the gene expression levels of the twenty-five selenoproteins and six HUB nodes in androgen receptor-positive (22RV1 and LNCaP) and androgen receptor–negative (DU145 and PC3) cell lines, compared to human nontransformed, and differentiated, prostate epithelial cells (EPN) by RT-qPCR analysis. This analysis confirmed that the combined evaluation of some selenoproteins and HUB nodes could have prognostic value and may improve patient outcome predictions.

An Integrated In Silico, In Vitro and Tumor Tissues Study Identified Selenoprotein S (SELENOS) and Valosin-Containing Protein (VCP/p97) as Novel Potential Associated Prognostic Biomarkers in Triple Negative Breast Cancer

“…In the present study, by integrating bothin silicoand wet lab approaches, we demonstrated that the expression profiles of five selenoproteins are specifically dysregulated in TNBC. Most importantly, by bioinformatics analysis, we selected SELENOS and its interacting protein VCP/p97 as inter-related with the others and whose coordinated overexpression is associated with poor prognosis in TNBC.Overall, we confirmed, as previously suggested [12], that only the combined evaluation of some selenoproteins and of HUB nodes could have prognostic value and may improve patient outcome prediction.…”

“…Recently, to better define the correlation between the selenoprotein family and cancer, we took advantage of a bioinformatics approach and studied the interaction network between all twenty-five selenoproteins, highlighting the presence of six HUB nodes (ABL1, EP300, FYN, MYC, PSMB2 and SRPK2) that play the strongest role in coordinating the obtained network. Within this analysis, we also analyzed the correlation between some selenoproteins and/or HUB node gene expression and patient outcome in ten solid tumors [12]. Moreover, we evaluated the gene expression levels of the twenty-five selenoproteins and of the six HUB nodes identified in four prostate cancer cell lines compared to normal prostate epithelial cells, selecting three selenoproteins (GPX2, EP300 and PSMB2), whose collective expression correlated with the overall survival of prostate cancer patients, suggesting that only the combined evaluation of some selenoproteins and HUB nodes could have prognostic value and may improve patient outcome prediction [12].…”

“…Within this analysis, we also analyzed the correlation between some selenoproteins and/or HUB node gene expression and patient outcome in ten solid tumors [12]. Moreover, we evaluated the gene expression levels of the twenty-five selenoproteins and of the six HUB nodes identified in four prostate cancer cell lines compared to normal prostate epithelial cells, selecting three selenoproteins (GPX2, EP300 and PSMB2), whose collective expression correlated with the overall survival of prostate cancer patients, suggesting that only the combined evaluation of some selenoproteins and HUB nodes could have prognostic value and may improve patient outcome prediction [12].…”