The role of immune checkpoint inhibitors: Variable number of tandem repeat (VNTR) polymorphism in the second exon of the P-selectin glycoprotein ligand-1 (PSGL-1) gene polymorphism in multiple myeloma.

IF 3 2区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY Molecular Carcinogenesis Pub Date : 2024-10-01 Epub Date: 2024-07-02 DOI:10.1002/mc.23787
Yasemin Oyaci, Mustafa Pehlivan, Sacide Pehlivan, Tahir Alper Cinli, Fatima Ceren Tuncel, Elif Ertas, Istemi Serin
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Abstract

Somatic mutations and polymorphisms may play a role in multiple myeloma (MM) susceptibility and survival. One of the immune checkpoint inhibitors is P-selectin glycoprotein ligand-1 (PSGL-1); the majority of tumor-infiltrating leukocytes express PSGL-1, causing T cell and immune inhibition via PSGL-1 mediator molecules. We aimed to investigate the effect of variable number of tandem repeat (VNTR) polymorphism in the second exon of the PSGL-1 gene on MM susceptibility, response to treatment and survival in our patient group. A total of 238 patients diagnosed with MM between January 2010 and January 2021 and 162 healthy individuals as a control group were included in this cross-sectional study. The genotypes of the VNTR polymorphism in the second exon of the PSGL-1 gene were statistically compared between patients and healthy controls; the statistically significant effects of the genotypes on response to first-line treatment and survival were examined. The AC genotype was significantly higher in healthy controls compared to patients diagnosed with MM (p < 0.001). The median PFS in patients with AA/AB/AC was 56 months, while it was 100 months in patients with BB/CC. The hazard ratio of 1.34 for PFS was found to be clinically significant and having the BB/CC genotype could provide a longer PFS compared to others, but it was not statistically significant due to the sample size. Our study results will shed light on new study plans in terms of immune checkpoint target therapies among conventional treatment preferences in MM.

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免疫检查点抑制剂的作用:多发性骨髓瘤中P-选择素糖蛋白配体-1(PSGL-1)基因第二外显子多态性的串联重复变异数(VNTR)。
体细胞突变和多态性可能对多发性骨髓瘤(MM)的易感性和存活率有影响。免疫检查点抑制剂之一是P-选择素糖蛋白配体-1(PSGL-1);大多数肿瘤浸润白细胞表达PSGL-1,通过PSGL-1介导分子导致T细胞和免疫抑制。我们的目的是研究 PSGL-1 基因第二外显子的可变串联重复数(VNTR)多态性对 MM 易感性、治疗反应和患者生存期的影响。这项横断面研究共纳入了238名在2010年1月至2021年1月期间确诊为MM的患者和162名健康人作为对照组。统计比较了患者和健康对照组之间PSGL-1基因第二外显子VNTR多态性的基因型,并考察了基因型对一线治疗反应和生存期的显著影响。与确诊为 MM 的患者相比,健康对照组的 AC 基因型明显较高(p
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来源期刊
Molecular Carcinogenesis
Molecular Carcinogenesis 医学-生化与分子生物学
CiteScore
7.30
自引率
2.20%
发文量
112
审稿时长
2 months
期刊介绍: Molecular Carcinogenesis publishes articles describing discoveries in basic and clinical science of the mechanisms involved in chemical-, environmental-, physical (e.g., radiation, trauma)-, infection and inflammation-associated cancer development, basic mechanisms of cancer prevention and therapy, the function of oncogenes and tumors suppressors, and the role of biomarkers for cancer risk prediction, molecular diagnosis and prognosis.
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