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Potential relationship between the selenoproteome and cancer.

ABSTRACT: The role of the selenoproteome, which is the collection of all proteins containing selenium in an organism, in cancer development, growth and progression requires further investigation, due to the importance of selenium in both cancer and immune system function. Data about the selenoproteome, including its differential expression, single nucleotide variations, copy number variations, methylation, pathways and overall survival (OS) in five leading types of cancer are available from the GSCALite website. Subsequent to the analysis of these datasets, it was revealed that there was increased expression of GPX3 in stomach adenocarcinoma and lung squamous cell carcinoma, SELENOV in oesophageal carcinoma, GPX8 and GPX4 in colon adenocarcinoma, TXNRD1 and SEPHS1 in hepatocellular carcinoma and GPX8 in lung adenocarcinoma were associated with poor survival. Decreased gene expression of SELENOP was indicated in liver hepatocellular carcinoma and GPX3, and SELENOW, SELENOK, SELENBP1 and SECISBP2 in lung adenocarcinoma were associated with a poor prognosis. OS data suggested that hypermethylation of GPX4 in colon adenocarcinoma, GPX8 in lung squamous cell carcinoma, GPX1 in stomach adenocarcinoma and GPX3 in lung adenocarcinoma was associated with low survival, as is hypomethylation of GPX5 in lung adenocarcinoma. The selenoproteome is heterogeneous, especially in its effect on the OS of patients with cancer. The present study demonstrated that the roles of GPX4 in colon adenocarcinoma, SCLY and SELENOV in oesophageal carcinoma, SEPHS1 in liver hepatocellular carcinoma, SELENOK in lung cancer, as well as SELENOM and SELENOW in stomach adenocarcinoma requires further research. The present study may lead to the identification of novel biomarkers or potential therapeutic targets for use in the treatment of cancers, such as colon adenocarcinoma, oesophageal carcinoma, liver hepatocellular carcinoma, lung cancer and stomach adenocarcinoma.

SUBMITTER: Jia Y

PROVIDER: S-EPMC7590431 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Potential relationship between the selenoproteome and cancer.

Jia Yi Y Dai Jie J Zeng Zhu Z

Molecular and clinical oncology 20201011 6

The role of the selenoproteome, which is the collection of all proteins containing selenium in an organism, in cancer development, growth and progression requires further investigation, due to the importance of selenium in both cancer and immune system function. Data about the selenoproteome, including its differential expression, single nucleotide variations, copy number variations, methylation, pathways and overall survival (OS) in five leading types of cancer are available from the GSCALite w ...[more]

PMID: 33133596

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Project description:BackgroundFucose is utilized for the modification of different molecules involved in blood group determination, immunological reactions, and signal transduction pathways. We have recently reported that enhanced activity of the fucosyltransferase 3 and/or 6 promoted TGF-ß-mediated epithelial mesenchymal transition and was associated with increased metastatic potential of colorectal cancer (CRC), suggesting that fucose is required by CRC cells. With this in mind, we examined requirement of L-fucose in CRC cells and developed fucose-bound nanoparticles as vehicles for delivery of anticancer drugs specific to CRC.MethodsIn this study, we first examined the expression of fucosylated proteins in 50 cases of CRC by immunochistochemical staining with biotinylated Aleuria aurantia lectin (AAL). Then we carried out an L-fucose uptake assay using three CRC cell lines. Finally, we developed fucose-bound nanoparticles as vehicles for the delivery of an anticancer drug, SN38, and examined tumor growth inhibition in mouse xenograft model (n = 6 mice per group). All statistical tests were two-sided.ResultsWe found a statistically significant relationship between vascular invasion, clinical stage, and intensity score of AAL staining (P≤ .02). L-fucose uptake assay revealed that L-fucose incorporation, as well as fucosylated protein release, was high in cells rich in fucosylated proteins. L-fucose-bound liposomes effectively delivered Cy5.5 into CRC cells. The excess of L-fucose decreased the efficiency of Cy5.5 uptake through L-fucose-bound liposomes, suggesting an L-fucose receptor dependency. Intravenously injected, L-fucose-bound liposomes carrying SN38 were successfully delivered to CRC cells, mediating efficient tumor growth inhibition (relative tumor growth ratio: no treatment group [NT], 8.29 ± 3.09; SN38-treated group [SN38], 3.53 ± 1.47; liposome-carrying, SN38-treated group [F0], 3.1 ± 1.39; L-fucose-bound, liposome-carrying, SN38-treated group [F50], 0.94 ± 0.89; F50 vs NT,P= .003; F50 vs SN38,P= .02, F50 vs F0,P= .04), as well as prolonging survival of mouse xenograft models (log-rank test,P< .001).ConclusionsThus, fucose-bound liposomes carrying anticancer drugs provide a new strategy for the treatment of CRC patients.

Project description:Pathogenic Potential (PP) is a mathematical description of an individual microbe, virus, or parasite's ability to cause disease in a host, given the variables of inoculum, signs of disease, mortality, and in some instances, median survival time of the host. We investigated the relationship between pathogenic potential (PP) and infective inoculum (I) using two pathogenic fungi in the wax moth Galleria mellonella with mortality as the relevant outcome. Our analysis for C. neoformans infection revealed negative exponential relationship between PP and I. Plotting the log(I) versus the Fraction of animals with signs or symptoms (Fs) over median host survival time (T) revealed a linear relationship, with a slope that varied between the different fungi studied and a y-intercept corresponding to the inoculum that produced no signs of disease. The I vs Fs/T slope provided a measure of the pathogenicity of each microbial species, which we call the pathogenicity constant or kPath. The kPath provides a new parameter to quantitatively compare the relative virulence and pathogenicity of microbial species for a given host. In addition, we investigated the PP and Fs/T from values found in preexisting literature. Overall, the relationship between Fs/T and PP versus inoculum varied among microbial species and extrapolation to zero signs of disease allowed the calculation of the lowest pathogenic inoculum (LPI) of a microbe. Microbes tended to fall into two groups: those with positive linear relationships between PP and Fs/T vs I, and those that had a negative exponential PP vs I relationship with a positive logarithmic Fs/T vs I relationship. The microbes with linear relationships tended to be bacteria, whereas the exponential-based relationships tended to be fungi or higher order eukaryotes. Differences in the type and sign of the PP vs I and Fs/T vs I relationships for pathogenic microbes suggest fundamental differences in host-microbe interactions leading to disease.

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Potential relationship between the selenoproteome and cancer.

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Potential relationship between the selenoproteome and cancer.

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