Počet záznamů: 1
Investigation of single and synergic effects of NLRC5 and PD-L1 variants on the risk of colorectal cancer
- 1.
SYSNO ASEP 0493626 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Investigation of single and synergic effects of NLRC5 and PD-L1 variants on the risk of colorectal cancer Author(s) Catalano, C. (DE)
da Silva Filho, M.I. (DE)
Frank, Ch. (DE)
Jirásková, Kateřina (UEM-P)
Vymetálková, Veronika (UEM-P) RID
Levý, M. (CZ)
Liška, V. (CZ)
Vyčítal, O. (CZ)
Naccarati, Alessio (UEM-P)
Vodičková, Ludmila (UEM-P) RID
Hemminki, K. (DE)
Vodička, Pavel (UEM-P) RID
Weber, A.N.R. (DE)
Försti, A. (DE)Article number e0192385 Source Title PLoS ONE. - : Public Library of Science - ISSN 1932-6203
Roč. 13, č. 2 (2018)Number of pages 13 s. Language eng - English Country US - United States Keywords class-i transactivator ; immune evasion ; t-cells ; expression ; colon Subject RIV EB - Genetics ; Molecular Biology OECD category Gastroenterology and hepatology R&D Projects NV15-26535A GA MZd - Ministry of Health (MZ) NV15-27580A GA MZd - Ministry of Health (MZ) Institutional support UEM-P - RVO:68378041 UT WOS 000424302800061 EID SCOPUS 85041646996 DOI https://doi.org/10.1371/journal.pone.0192385 Annotation Constitutive activation of interferon signaling pathways has been reported in colorectal cancer leading to a strong CD8+ T cell response through stimulation of NLRC5 expression. Primed CD8+ T cell expansion, however, may be negatively regulated by PD-L1 expression. Additionally, aberrant PD-L1 expression enables cancer cells to escape the immune attack. Our study aimed to select potential regulatory variants in the NLRC5 and PD-L1 genes by using several online in silico tools, such as UCSC browser, HaploReg, Regulome DB, Gtex Portal, microRNA and transcription factor binding site prediction tools and to investigate their influence on colorectal cancer risk in a Czech cohort of 1424 patients and 1114 healthy controls. Logistic regression analysis adjusted for age and gender reported a moderate association between rectal cancer risk and two NLRC5 SNPs, rs1684575 T>G and rs3751710. Given that a combination of genetic variants, rather than a single polymorphism, may explain better the genetic etiology of colorectal cancer, we studied the interplay between the variants within NLRC5, PD-L1 and the previously genotyped IFNGR1 and IFNGR2variants, to evaluate their involvement in the risk of colorectal cancer development. Overall we obtained 18 pair wise interactions within and between the NLRC5ad PD-L1 genes and 6 more when IFNGR variants were added. Our data suggest that not only a single genetic variant but also an interaction between two or more variants within genes involved in immune regulation may play important roles in the onset of colorectal cancer, providing therefore novel biological information, which could eventually improve colorectal cancer risk management but also PD-1-based immunotherapy of colorectal cancer. Workplace Institute of Experimental Medicine Contact Arzuv Čaryjeva, arzuv.caryjeva@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Year of Publishing 2019
Počet záznamů: 1