The LGALS1 gene polymorphism is not associated with galectin-1 levels in tumor tissue and blood of colon cancer patients

O. Urazova, G. V. Reyngardt, Yuliya V. Kolobovnikova, A. V. Kurnosenko, V. S. Poletika, Olga A. Vasil'yeva, A. Avgustinovich
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Abstract

Background: Galectin-1 plays an important role in the pathogenesis of colorectal cancer (CRC). The blood and tumoral levels of galectin-1 could be dependent on the polymorphism of the promotor region of LGALS1 gene. Aim: To analyze an association between galectin-1 levels in tumor tissue and plasma and the genotype of the rs4820293 and rs4820294 polymorphisms of the LGALS1 gene in CRC patients. Materials and methods: The study included a total of 70 inpatients with pathologically verified CRC (International Classification of Diseases 10th Revision codes C18-C20, 39 men and 31 women, mean age 65.4 ± 5.7 years), who were receiving treatment in the Tomsk Regional Oncology Center and Cancer Research Institute of the Tomsk National Research Medical Center from 2020 to 2022. The control group consisted of 70 healthy volunteers (34 men and 36 women, mean age 62.3 ± 7.2 years). Venous blood samples were taken from all study participants and tumor tissue samples were obtained from the CRC patients. Galectin-1 expression in the tumor tissue was assessed by immunohistochemistry and plasma galectin-1 levels by enzyme-linked immunosorbent assay. The LGALS1 gene polymorphisms rs4820293 and rs4820294 were identified by restriction fragment length polymorphism analysis. Results: The distributions of genotype and allele frequencies of polymorphic variants rs4820293 and rs4820294 of the LGALS1 gene in the CRC patients and in the healthy donors were comparable (p 0.05). Calculation of odds ratios did not confirm any association between LGALS1 gene polymorphisms and CRC. However, the rs4820294 polymorphism had a strong association with regional metastasis and tumor differentiation grade (Cramer's V above 0.4, p 0.001). The plasma galectin-1 levels in the CRC patients with the AA genotype of the rs4820294 polymorphism were higher than in the healthy carriers (17.42 versus 12.92 ng/ml, p = 0.040). However, there were no significant differences in the content of galectin-1+ cells in the tumor and galectin-1 in plasma of the CRC patients depending on the genotype of the LGALS1 gene polymorphisms (p 0.05). Conclusion: The LGALS1 gene polymorphism is not associated with CRC, but in the carriers of the rs4820294 variant is related to clinical and morphological parameters of the tumor process. The intratumoral expression and blood levels of galectin-1 in CRC patients are not dependent on the genotype of rs4820293 and rs4820294 polymorphisms of the LGALS1 gene.
LGALS1 基因多态性与结肠癌患者肿瘤组织和血液中的 galectin-1 水平无关
背景:Galectin-1 在结直肠癌(CRC)的发病机制中发挥着重要作用。血液和肿瘤中 galectin-1 的水平可能取决于 LGALS1 基因启动子区的多态性。目的:分析 CRC 患者肿瘤组织和血浆中 galectin-1 水平与 LGALS1 基因 rs4820293 和 rs4820294 多态性基因型之间的关联。材料和方法:研究对象包括 2020 年至 2022 年期间在托木斯克地区肿瘤中心和托木斯克国家研究医疗中心癌症研究所接受治疗的 70 名经病理证实的 CRC 住院患者(国际疾病分类第 10 次修订代码 C18-C20,男性 39 人,女性 31 人,平均年龄 65.4 ± 5.7 岁)。对照组包括 70 名健康志愿者(34 名男性和 36 名女性,平均年龄为 62.3 ± 7.2 岁)。研究人员采集了所有参与者的静脉血样本,并从 CRC 患者身上采集了肿瘤组织样本。肿瘤组织中 Galectin-1 的表达通过免疫组化法进行评估,血浆中 galectin-1 的水平通过酶联免疫吸附法进行评估。通过限制性片段长度多态性分析确定了 LGALS1 基因多态性 rs4820293 和 rs4820294。结果显示LGALS1基因多态性变异rs4820293和rs4820294在CRC患者和健康供体中的基因型和等位基因频率分布相当(P 0.05)。计算几率比值并未证实 LGALS1 基因多态性与 CRC 之间存在任何关联。然而,rs4820294 多态性与区域转移和肿瘤分化等级有密切关系(Cramer's V 高于 0.4,P 0.001)。具有 rs4820294 多态性 AA 基因型的 CRC 患者的血浆 galectin-1 水平高于健康携带者(17.42 对 12.92 ng/ml,P = 0.040)。然而,根据 LGALS1 基因多态性基因型的不同,肿瘤中 galectin-1+ 细胞的含量和 CRC 患者血浆中 galectin-1 的含量没有明显差异(P 0.05)。结论LGALS1基因多态性与CRC无关,但rs4820294变异携带者的LGALS1基因多态性与肿瘤过程的临床和形态学参数有关。CRC 患者瘤内 galectin-1 的表达和血液水平与 LGALS1 基因 rs4820293 和 rs4820294 多态性的基因型无关。
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