PD-L1/CD274 基因变异的阻断信号及其对肺癌易感性的潜在影响。
The blockage signal for PD-L1/CD274 gene variants and their potential impact on lung carcinoma susceptibility.
发表日期:2023 Nov 06
作者:
Mohamed I Sakran, Adel I Alalawy, Amnah A Alharbi, Mohamed E El-Hefnawy, Salem M Alzahrani, Ahmed Alfuraydi, Fahad Mohammed Alzuaibr, Nahla S Zidan, Afaf M Elsaid, Eman A Toraih, Rami M Elshazli
来源:
INTERNATIONAL IMMUNOPHARMACOLOGY
摘要:
程序性死亡配体 1 (PD-L1/CD274) 基因通过与受刺激的 T 淋巴细胞上的受体 PD-1 结合,在抑制抗肿瘤免疫方面发挥关键功能。然而,不同人群与肺部易感性之间的强关联仍不清楚。本研究的暂定目的是利用极权主义技术(包括遗传分析和复杂的生物信息学方法)研究 PD-L1/CD274 多态性是否调节肺癌易感性。对 PD-L1/CD274(rs822336、rs2297136 和 rs4143815)变异体进行基因分型使用四引物 ARMS-PCR 在 126 例肺癌病例和 117 例健康对照中进行了研究。 Logistic 回归和生物信息学分析评估了遗传关联。rs2297136 GA 基因型与 GG 基因型相比,显着增加了肺癌风险 3.7 倍(OR 3.69,95% CI 1.39-9.81,p = 0.016),次要 A 等位基因也增加了风险(或 1.47,p = 0.044)。相比之下,与 GG 相比,rs4143815 CC 基因型与癌症风险降低 70% 相关(OR 0.30,95% CI 0.11-0.87,p = 0.012),尽管次要 C 等位基因本身并不显着。 rs822336 变体显示没有关联。单倍型和多变量分析支持了这些发现。计算机预测表明对 PD-L1 表达和活性的功能影响。这项研究发现了埃及人的 PD-L1/CD274 多态性与肺癌易感性之间的新关联。 rs2297136 变异增加了风险,而 rs4143815 变异则提供保护,强调 PD-1/PD-L1 轴作为肺肿瘤发生中的潜在生物标志物和治疗靶点。需要在更大的队列和功能研究中进行复制。版权所有 © 2023 Elsevier B.V. 保留所有权利。
The programmed death-ligand 1 (PD-L1/CD274) gene plays a key function in suppressing anti-tumor immunity through binding to its receptor PD-1 on stimulated T lymphocytes. However, robust associations among diverse populations and lung susceptibility remain unclear. The tentative purpose of this research is to investigate whether PD-L1/CD274 polymorphisms modulate susceptibility to lung carcinoma using totalitarian techniques, including genetic analysis, and sophisticated bioinformatic methods.PD-L1/CD274 (rs822336, rs2297136, and rs4143815) variants were genotyped in 126 lung carcinoma cases and 117 healthy controls using tetra-primer ARMS-PCR. Logistic regression and bioinformatics analyses assessed genetic associations.The rs2297136 GA genotype significantly increased lung cancer risk by 3.7-fold versus GG genotype (OR 3.69, 95 % CI 1.39-9.81, p = 0.016), with the minor A allele also increasing risk (OR 1.47, p = 0.044). In contrast, the rs4143815 CC genotype was associated with 70 % decreased cancer risk versus GG (OR 0.30, 95 % CI 0.11-0.87, p = 0.012), although the minor C allele itself was not significant. The rs822336 variant showed no association. Haplotype and multivariate analyses supported these findings. In silico predictions suggested functional impacts on PD-L1 expression and activity.This study identified novel associations between PD-L1/CD274 polymorphisms and susceptibility to lung cancer in Egyptians. The rs2297136 variant increased risk while the rs4143815 variant conferred protection, highlighting the PD-1/PD-L1 axis as a potential biomarker and therapeutic target in lung oncogenesis. Replication in larger cohorts and functional studies are warranted.Copyright © 2023 Elsevier B.V. All rights reserved.