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The Variations' in Genes Encoding TIM-3 and Its Ligand, Galectin-9, Influence on ccRCC Risk and Prognosis
Anna Andrzejczak1, Krzysztof Tupikowski2, Anna Tomkiewicz1
1Laboratory of Genetics and Epigenetics of Human Diseases, Department of Experimental Therapy, Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, 53-114 Wrocław, Poland.
Abstract:
Renal cell cancer is the most common type of kidney cancer in adults, and clear cell renal cell carcinoma (ccRCC) is the most diagnosed type. T cell immunoglobulin and mucin-domain-containing-3 (TIM-3) belongs to immunological checkpoints that are key regulators of the immune response. One of the known TIM-3 ligands is galectin-9 (LGALS9). A limited number of studies have shown an association between TIM-3 polymorphisms and cancer risk in the Asian population; however, there is no study on the role of LGALS9 polymorphisms in cancer. The present study aimed to analyze the influence of TIM-3 and LGALS9 polymorphisms on susceptibility to ccRCC and patient overall survival (OS), with over ten years of observations. Using TaqMan probes, ARMS-PCR, and RFPL-PCR, we genotyped two TIM-3 single-nucleotide polymorphisms (SNPs): rs1036199 and rs10057302, and four LGALS9 SNPs: rs361497, rs3751093, rs4239242, and rs4794976. We found that the presence of the rs10057302 A allele (AC + AA genotypes) as well as the rs4794976 T allele (GT + TT genotypes) decreased susceptibility to ccRCC by two-fold compared to corresponding homozygotes. A subgroup analysis showed the association of some SNPs with clinical features. Moreover, TIM-3 rs1036199 significantly influenced OS. Our results indicate that variations within TIM-3 and LGALS9 genes are associated with ccRCC risk and OS.
Insights
Genetic variations in TIM-3 and LGALS9 influence clear cell renal cell carcinoma (ccRCC) risk and patient survival. Specific polymorphisms in TIM-3 and LGALS9 were found to decrease ccRCC susceptibility and impact overall survival.
Area of Science:
- Immunogenetics
- Oncology
- Molecular Biology
Background:
- Clear cell renal cell carcinoma (ccRCC) is the most common kidney cancer.
- T cell immunoglobulin and mucin-domain-containing-3 (TIM-3) and its ligand galectin-9 (LGALS9) are key immune checkpoints.
- Limited research exists on the role of LGALS9 polymorphisms in cancer risk.
Purpose of the Study:
- To investigate the association between TIM-3 and LGALS9 gene polymorphisms and ccRCC susceptibility.
- To evaluate the impact of these polymorphisms on patient overall survival (OS).
- To analyze the relationship between specific SNPs and clinical features in ccRCC patients.
Main Methods:
- Genotyping of two TIM-3 SNPs (rs1036199, rs10057302) and four LGALS9 SNPs (rs361497, rs3751093, rs4239242, rs4794976) using TaqMan probes, ARMS-PCR, and RFPL-PCR.
- Analysis of ccRCC susceptibility and overall survival (OS) in relation to identified genotypes.
- Subgroup analysis to correlate SNPs with clinical characteristics.
Main Results:
- The rs10057302 A allele in TIM-3 and the rs4794976 T allele in LGALS9 were associated with a two-fold decrease in ccRCC susceptibility.
- Specific SNPs showed associations with clinical features of ccRCC.
- The TIM-3 rs1036199 polymorphism significantly influenced patient overall survival.
Conclusions:
- Genetic variations in TIM-3 and LGALS9 are linked to both susceptibility to ccRCC and patient outcomes.
- These findings highlight the potential role of immunogenetic factors in ccRCC development and prognosis.
- Further research into these polymorphisms could inform personalized risk assessment and treatment strategies for ccRCC.
