关键词: DIO1 GPX3 KIRC LRRC19 fatty acid degradation renal clear cell carcinoma selenium selenium adjuvant therapy selenoprotein

Mesh : Antioxidants / pharmacology Biomarkers, Tumor / genetics metabolism Carcinoma, Renal Cell / drug therapy genetics metabolism pathology Chemotherapy, Adjuvant / mortality Cohort Studies Data Mining / methods Follow-Up Studies Gene Expression Regulation, Neoplastic Glutathione Peroxidase / genetics metabolism Humans Iodide Peroxidase / genetics metabolism Kidney Neoplasms / drug therapy genetics metabolism pathology Prognosis Receptors, Cell Surface / genetics metabolism Selenium / pharmacology Selenoproteins / genetics metabolism Survival Rate

来  源:   DOI:10.3390/genes11040440   PDF(Sci-hub)   PDF(Pubmed)

Abstract:
Kidney renal clear cell carcinoma (KIRC) is the most common and fatal subtype of renal cancer. Antagonistic associations between selenium and cancer have been reported in previous studies. Selenium compounds, as anti-cancer agents, have been reported and approved for clinical trials. The main active form of selenium in selenoproteins is selenocysteine (Sec). The process of Sec biosynthesis and incorporation into selenoproteins plays a significant role in biological processes, including anti-carcinogenesis. However, a comprehensive selenoprotein mRNA analysis in KIRC remains absent. In the present study, we examined all 25 selenoproteins and identified key selenoproteins, glutathione peroxidase 3 (GPX3) and type 1 iodothyronine deiodinase (DIO1), with the associated prognostic biomarker leucine-rich repeat containing 19 (LRRC19) in clear cell renal cell carcinoma cases from The Cancer Genome Atlas (TCGA) database. We performed validations for the key gene expression levels by two individual clear cell renal cell carcinoma cohorts, GSE781 and GSE6344, datasets from the Gene Expression Omnibus (GEO) database. Multivariate survival analysis demonstrated that low expression of LRRC19 was an independent risk factor for OS. Gene set enrichment analysis (GSEA) identified tyrosine metabolism, metabolic pathways, peroxisome, and fatty acid degradation as differentially enriched with the high LRRC19 expression in KIRC cases, which are involved in selenium therapy of clear cell renal cell carcinoma. In conclusion, low expression of LRRC19 was identified as an independent risk factor, which will advance our understanding concerning the selenium adjuvant therapy of clear cell renal cell carcinoma.
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