The Variations’ in Genes Encoding TIM-3 and Its Ligand, Galectin-9, Influence on ccRCC Risk and Prognosis
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 kn...
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MDPI AG
2023-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/3/2042 |
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| author | Anna Andrzejczak Krzysztof Tupikowski Anna Tomkiewicz Bartosz Małkiewicz Kuba Ptaszkowski Aleksandra Domin Tomasz Szydełko Lidia Karabon |
| author_facet | Anna Andrzejczak Krzysztof Tupikowski Anna Tomkiewicz Bartosz Małkiewicz Kuba Ptaszkowski Aleksandra Domin Tomasz Szydełko Lidia Karabon |
| author_sort | Anna Andrzejczak |
| collection | DOAJ |
| description | 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 (<i>LGALS9</i>). A limited number of studies have shown an association between <i>TIM-3</i> polymorphisms and cancer risk in the Asian population; however, there is no study on the role of <i>LGALS9</i> polymorphisms in cancer. The present study aimed to analyze the influence of <i>TIM-3</i> and <i>LGALS9</i> 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 <i>TIM-3</i> single-nucleotide polymorphisms (SNPs): rs1036199 and rs10057302, and four <i>LGALS9</i> 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, <i>TIM-3</i> rs1036199 significantly influenced OS. Our results indicate that variations within <i>TIM-3</i> and <i>LGALS9</i> genes are associated with ccRCC risk and OS. |
| first_indexed | 2024-03-11T09:43:14Z |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T09:43:14Z |
| publishDate | 2023-01-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-cf4c409d84a0413a9a47db8bc58d91942023-11-16T16:51:30ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-01-01243204210.3390/ijms24032042The Variations’ in Genes Encoding TIM-3 and Its Ligand, Galectin-9, Influence on ccRCC Risk and PrognosisAnna Andrzejczak0Krzysztof Tupikowski1Anna Tomkiewicz2Bartosz Małkiewicz3Kuba Ptaszkowski4Aleksandra Domin5Tomasz Szydełko6Lidia Karabon7Laboratory 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, PolandSubdivision of Urology, Lower Silesian Center for Oncology, Pulmonology and Hematology, 53-413 Wrocław, PolandLaboratory 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, PolandUniversity Center of Excellence in Urology, Department of Minimally Invasive and Robotic Urology, Wroclaw Medical University, 50-556 Wrocław, PolandDepartment of Clinical Biomechanics and Physiotherapy in Motor System Disorders, Wrocław Medical University, 50-556 Wrocław, PolandLaboratory 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, PolandUniversity Center of Excellence in Urology, Department of Minimally Invasive and Robotic Urology, Wroclaw Medical University, 50-556 Wrocław, PolandLaboratory 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, PolandRenal 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 (<i>LGALS9</i>). A limited number of studies have shown an association between <i>TIM-3</i> polymorphisms and cancer risk in the Asian population; however, there is no study on the role of <i>LGALS9</i> polymorphisms in cancer. The present study aimed to analyze the influence of <i>TIM-3</i> and <i>LGALS9</i> 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 <i>TIM-3</i> single-nucleotide polymorphisms (SNPs): rs1036199 and rs10057302, and four <i>LGALS9</i> 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, <i>TIM-3</i> rs1036199 significantly influenced OS. Our results indicate that variations within <i>TIM-3</i> and <i>LGALS9</i> genes are associated with ccRCC risk and OS.https://www.mdpi.com/1422-0067/24/3/2042TIM-3HAVCR2galectin-9 (<i>LGALS9</i>)clear cell renal cell carcinoma (ccRCC)single-nucleotide gene polymorphism (SNP)immunological checkpoint |
| spellingShingle | Anna Andrzejczak Krzysztof Tupikowski Anna Tomkiewicz Bartosz Małkiewicz Kuba Ptaszkowski Aleksandra Domin Tomasz Szydełko Lidia Karabon The Variations’ in Genes Encoding TIM-3 and Its Ligand, Galectin-9, Influence on ccRCC Risk and Prognosis International Journal of Molecular Sciences TIM-3 HAVCR2 galectin-9 (<i>LGALS9</i>) clear cell renal cell carcinoma (ccRCC) single-nucleotide gene polymorphism (SNP) immunological checkpoint |
| title | The Variations’ in Genes Encoding TIM-3 and Its Ligand, Galectin-9, Influence on ccRCC Risk and Prognosis |
| title_full | The Variations’ in Genes Encoding TIM-3 and Its Ligand, Galectin-9, Influence on ccRCC Risk and Prognosis |
| title_fullStr | The Variations’ in Genes Encoding TIM-3 and Its Ligand, Galectin-9, Influence on ccRCC Risk and Prognosis |
| title_full_unstemmed | The Variations’ in Genes Encoding TIM-3 and Its Ligand, Galectin-9, Influence on ccRCC Risk and Prognosis |
| title_short | The Variations’ in Genes Encoding TIM-3 and Its Ligand, Galectin-9, Influence on ccRCC Risk and Prognosis |
| title_sort | variations in genes encoding tim 3 and its ligand galectin 9 influence on ccrcc risk and prognosis |
| topic | TIM-3 HAVCR2 galectin-9 (<i>LGALS9</i>) clear cell renal cell carcinoma (ccRCC) single-nucleotide gene polymorphism (SNP) immunological checkpoint |
| url | https://www.mdpi.com/1422-0067/24/3/2042 |
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