4.7 Article

The blockage signal for PD-L1/CD274 gene variants and their potential impact on lung carcinoma susceptibility

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INTERNATIONAL IMMUNOPHARMACOLOGY
卷 125, 期 -, 页码 -

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DOI: 10.1016/j.intimp.2023.111180

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PD-L1/CD274 variants; Single nucleotide variants; Genetic mutations; Lung carcinoma

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This study identified novel associations between PD-L1/CD274 polymorphisms and susceptibility to lung cancer in Egyptians, with the rs2297136 variant increasing risk and the rs4143815 variant conferring protection. These findings highlight the importance of the PD-1/PD-L1 axis as a potential biomarker and therapeutic target in lung oncogenesis.
Background: 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.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.Results: 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.Conclusions: 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.

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