LRRC19—A Bridge between Selenium Adjuvant Therapy and Renal Clear Cell Carcinoma: A Study Based on Datamining

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.

Multi-database analysis showed that genes associated with inflammatory response are important for prognosis prediction of renal clear cell carcinoma

“…[27][28][29] Similarly, the other IRGMS mentioned in this study have also been shown to be strongly associated with various tumors in previous studies. [30][31][32][33][34][35][36][37][38][39][40][41] 5 Conclusion…”

Genes associated with inflammation for prognosis prediction for clear cell renal cell carcinoma: a multi-database analysis

“…The protein product of LRRC19 is specifically expressed in the kidney, spleen, and intestine and is involved in local inflammatory responses ( 70 ). In addition, LRRC19 is associated with the prognosis and adjuvant treatment of ccRCC ( 71 , 72 ). As a member of the prominin family, PROM1 is often considered a biomarker for cancer stem cells ( 73 ).…”

Downregulation of LRRC19 Is Associated with Poor Prognosis in Colorectal Cancer

“…This study showed that the LRRC19 protein appears to be specifically expressed in the kidney, spleen, and intestine [ 31 ]. Liu et al reported that the reduced expression of LRRC19 was an independent risk factor for OS and LRRC19 could serve as a novel biomarker for prognosis and adjuvant treatment of selenium [ 32 ]. Chai et al proposed that LRRC19 can activate NF-kB and induce the expression of pro-inflammatory cytokines and is involved in the response to local inflammation [ 31 ].…”