Gene expression of programmed cell death ligand-1 (PDL-1) and vitamin D receptor (VDR) with the serum vitamin D3 in lung cancer

Salama, Ragaa H. M.; Faied, Soad M. A.; Elkholy, Maha; Abd-Elmawgoud, Norhan S.; Alsanory, Tasneem A; Alsanory, Aya A; Abd-Elmoniem, Ahmed A.; Abd-Elmawgoud, Mohamed S.; Mahmoud, Hanaa I.; Abdel-Qawy, Abdel-Rahman H.; Dahpy, Marwa A.

doi:10.1186/s43168-022-00168-0

Cited by 3 publications

(1 citation statement)

References 34 publications

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“…Altered levels of these toxins are thought to be involved in lung cancer pathogenesis. Increased VDR expression in lung cancer has been correlated with improved survival ( Salama et al, 2022 ). Genetic variants within the VDR gene might potentially influence the binding of 1,25(OH) 2 D and subsequently alter vitamin D levels and lung cancer pathogenesis ( Haznadar et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Revealing the association between vitamin D metabolic pathway gene variants and lung cancer risk: a systematic review and meta-analysis

Elsalahaty,

Alkafaas,

Bashir

et al. 2024

Front. Genet.

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Lung cancer is a crucial global issue, with more than one million deaths annually. While smoking is considered the main etiology of the disease, several genetic variants are associated with it. Alterations in vitamin D pathway genes have also been studied in regards to lung cancer, but the findings have been inconclusive. We here present a systematic review and meta-analysis of seven genes in this pathway: CYP2R1, CYP27B1, CYP24A1, CYP3A4, CYP3A5, GC, and VDR. Four databases (PubMed, Scopus, Cochrane Library, and Web of Science (WOS) databases) were searched. From these, 16 eligible case–control studies comprising 6,206 lung cancer cases and 7,272 health controls were obtained. These studies were subjected to comprehensive data extraction and quality scoring, and the pooled odds ratio with a 95% confidence interval was calculated to estimate the effect of each variant along with heterogeneity analysis and a risk of bias assessment. Our meta-analysis revealed an association between CYP3A4 (rs2740574) and lung cancer in the allelic, heterozygous, and dominant models. In addition, both VDR (Fok1: rs2228570) and VDR (Cdx-2: rs11568820) displayed a protective role in lung cancer development in the heterozygous and dominant models. Furthermore, VDR (Taq1: rs731236) showed a decreased risk of lung cancer in the allelic, homozygous, and recessive models. Similarly, VDR (BsmI: rs1544410) had a positive effect on lung cancer risk when subjected to allelic and recessive models. Our meta-analysis revealed the lack of association of CYP2R1 (rs10741657), CYP27B1 (rs3782130), CYP27B1 (rs10877012), CYP24A1 (rs6068816), CYP24A1 (rs4809960), CYP3A5 (rs776746), GC (rs7041), GC (rs4588), and VDR (ApaI: rs7975232) with lung cancer. Our work revealed that CYP3A4 (rs2740574) can represent an independent risk factor for lung cancer. This conclusion can aid better personalized medicine for lung cancer management, while further assessment for genetic variants of CYP3A4, CYP27B1, CYP24A1, GC, and VDR is still required to address more robust evidence.

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Section: Introductionmentioning

confidence: 99%

Revealing the association between vitamin D metabolic pathway gene variants and lung cancer risk: a systematic review and meta-analysis

Elsalahaty,

Alkafaas,

Bashir

et al. 2024

Front. Genet.

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Emerging perspectives: unraveling the anticancer potential of vitamin D3

Wakle,

Mokale,

Sakle

2023

Naunyn-Schmiedeberg's Arch Pharmacol

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Significance of NotchScore and JAG1 in predicting prognosis and immune response of low-grade glioma

Shi,

Ge,

Cai

et al. 2023

Front. Immunol.

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IntroductionLow-grade glioma (LGG) is a prevalent malignant tumor in the intracranial region. Despite the advancements in treatment methods for this malignancy over the past decade, significant challenges still persist in the form of drug resistance and tumor recurrence. The Notch signaling pathway plays essential roles in many physiological processes as well as in cancer development. However, the significance of the pathway and family genes in LGG are poorly understood. MethodsWe conducted gene expression profiling analysis using the TCGA dataset to investigate the gene set associated with the Notch signaling pathway. we have proposed a metric called "NotchScore" that quantifies the strength of the Notch signaling pathway and enables us to assess its significance in predicting prognosis and immune response in LGG. We downregulated JAG1 in low-grade gliomas to assess its influence on the proliferation and migration of these tumors. Ultimately, we determined the impact of the transcription factor VDR on the transcription of PDL1 through chip-seq data analysis.ResultsOur findings indicate that tumors with a higher NotchScore, exhibit poorer prognosis, potentially due to their ability to evade the anti-tumor effects of immune cells by expressing immune checkpoints. Among the genes involved in the Notch signaling pathway, JAG1 has emerged as the most representative in terms of capturing the characteristics of both NotchScore and Notch pathways. The experimental results demonstrate that silencing JAG1 yielded a significant decrease in tumor cell proliferation in LGG cell lines. Our study revealed mechanisms by which tumors evade the immune system through the modulation of PDL1 transcription levels via the PI3K-Akt signaling pathway. Additionally, JAG1 potentially influences PDL1 in LGG by regulating the PI3K-Akt signaling pathway and the expression of the transcription factor VDR.DiscussionThese findings contribute to our understanding of immune evasion by tumors in LGG. The insights gained from this research may have implications for the development of therapeutic interventions for LGG.

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Gene expression of programmed cell death ligand-1 (PDL-1) and vitamin D receptor (VDR) with the serum vitamin D3 in lung cancer

Cited by 3 publications

References 34 publications

Revealing the association between vitamin D metabolic pathway gene variants and lung cancer risk: a systematic review and meta-analysis

Revealing the association between vitamin D metabolic pathway gene variants and lung cancer risk: a systematic review and meta-analysis

Emerging perspectives: unraveling the anticancer potential of vitamin D3

Significance of NotchScore and JAG1 in predicting prognosis and immune response of low-grade glioma

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