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基因编码 TIM-3 及其配体半乳糖凝集素-9 的变异影响 ccRCC 的风险和预后。

The Variations' in Genes Encoding TIM-3 and Its Ligand, Galectin-9, Influence on ccRCC Risk and Prognosis.

机构信息

Laboratory 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.

Subdivision of Urology, Lower Silesian Center for Oncology, Pulmonology and Hematology, 53-413 Wrocław, Poland.

出版信息

Int J Mol Sci. 2023 Jan 20;24(3):2042. doi: 10.3390/ijms24032042.

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 (). A limited number of studies have shown an association between polymorphisms and cancer risk in the Asian population; however, there is no study on the role of polymorphisms in cancer. The present study aimed to analyze the influence of and 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 single-nucleotide polymorphisms (SNPs): rs1036199 and rs10057302, and four 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, rs1036199 significantly influenced OS. Our results indicate that variations within and genes are associated with ccRCC risk and OS.

摘要

肾细胞癌是成人中最常见的肾癌类型,透明细胞肾细胞癌(ccRCC)是最常见的诊断类型。T 细胞免疫球蛋白和粘蛋白结构域包含 3(TIM-3)属于免疫检查点,是免疫反应的关键调节剂。已知的 TIM-3 配体之一是半乳糖凝集素-9()。少数研究表明,在亚洲人群中,多态性与癌症风险之间存在关联;然而,目前尚无关于多态性在癌症中的作用的研究。本研究旨在分析和 多态性对 ccRCC 易感性和患者总生存期(OS)的影响,观察时间超过十年。使用 TaqMan 探针、ARMS-PCR 和 RFPL-PCR,我们对两个 单核苷酸多态性(SNPs):rs1036199 和 rs10057302 以及四个 SNPs:rs361497、rs3751093、rs4239242 和 rs4794976 进行了基因分型。我们发现,与相应的纯合子相比,rs10057302 A 等位基因(AC+AA 基因型)以及 rs4794976 T 等位基因(GT+TT 基因型)的存在使 ccRCC 的易感性降低了两倍。亚组分析显示,一些 SNP 与临床特征有关。此外,rs1036199 显著影响 OS。我们的结果表明,和 基因内的变异与 ccRCC 风险和 OS 相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59db/9917084/c5f43fbb3664/ijms-24-02042-g001.jpg

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