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miRNA 调控基因在 35 例散发性肺癌肿瘤中的变异分析。

Variant Analysis of miRNA Regulatory Genes in 35 Sporadic Lung Carcinoma Tumors.

机构信息

Department of Medical Genetics, Selcuk University, School of Medicine, Konya, Turkey.

出版信息

Dokl Biochem Biophys. 2023 Dec;513(Suppl 1):S1-S7. doi: 10.1134/S1607672924600052. Epub 2024 Mar 12.

Abstract

UNLABELLED

Lung cancer is one of the cancer types with the highest mortality worldwide. The most frequently mutated genes known to be clinically important in lung cancers are EGFR, BRAF, and KRAS genes. Therefore, the therapeutic agents developed are directed against variants that cause over-activation of the EGFR-KRAS-BRAF-BRAF-MEK/ERK signalling pathway. However, different responses of patients to Tyrosine Kinase Inhibitors (TKIs) suggest that new prognostic biomarkers should be defined and epigenetic mechanisms may be related to this situation.

METHODS

In this study, sequence analyses of AGO2, DICER, and DROSHA genes involved in miRNA biogenesis and EGFR, KRAS, and BRAF genes were performed in 35 patients with sporadic lung cancer.

RESULTS

We found variations in genes involved in miRNA biogenesis that have not been previously reported in the literature. In addition, we found 4 different variants in the EGFR gene that have been described in the literature. In addition, a statistically significant association was found between the presence of mutations in at least one of the genes involved in miRNA biogenesis and metastasis (p:0.02).

CONCLUSIONS

In conclusion, genomic dysregulation of key miRNA biogenesis genes may be one of the possible reasons for the differential response of patients to therapeutic agents and the development of metastasis in EGFR wild type tumours.

摘要

非特异性

肺癌是全球死亡率最高的癌症类型之一。在肺癌中,已知最常发生突变且具有临床重要性的基因是 EGFR、BRAF 和 KRAS 基因。因此,开发的治疗药物针对导致 EGFR-KRAS-BRAF-BRAF-MEK/ERK 信号通路过度激活的变体。然而,患者对酪氨酸激酶抑制剂 (TKI) 的不同反应表明,应该定义新的预后生物标志物,并且表观遗传机制可能与这种情况有关。

方法

在这项研究中,对 35 名散发型肺癌患者的 miRNA 生物发生中涉及 AGO2、DICER 和 DROSHA 基因以及 EGFR、KRAS 和 BRAF 基因进行了序列分析。

结果

我们发现了以前在文献中未报道过的 miRNA 生物发生中涉及的基因的变异。此外,我们在 EGFR 基因中发现了 4 种不同的变体,这些变体已在文献中描述过。此外,还发现 miRNA 生物发生中至少有一个基因发生突变与转移之间存在统计学显著关联(p:0.02)。

结论

总之,关键 miRNA 生物发生基因的基因组失调可能是患者对治疗药物反应不同和 EGFR 野生型肿瘤转移发展的原因之一。

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