35 例散发性肺癌肿瘤中 miRNA 调控基因的变异分析

IF 0.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Doklady Biochemistry and Biophysics Pub Date : 2024-03-12 DOI:10.1134/S1607672924600052
Özkan Bağcı, Ebru Marzioğlu Özdemir, Batuhan Şanlıtürk
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引用次数: 0

摘要

肺癌是全球死亡率最高的癌症类型之一。已知在肺癌临床上最常见的突变基因是表皮生长因子受体(EGFR)、BRAF 和 KRAS 基因。因此,开发的治疗药物都是针对导致表皮生长因子受体-KRAS-BRAF-BRAF-MEK/ERK 信号通路过度激活的变异基因。然而,患者对酪氨酸激酶抑制剂(TKIs)的不同反应表明,应该定义新的预后生物标志物,而表观遗传机制可能与这种情况有关:本研究对35例散发性肺癌患者中参与miRNA生物发生的AGO2、DICER和DROSHA基因以及EGFR、KRAS和BRAF基因进行了序列分析:结果:我们在参与 miRNA 生物发生的基因中发现了以前文献中未报道过的变异。此外,我们还在表皮生长因子受体(EGFR)基因中发现了 4 种不同的变异,这些变异已在文献中有所描述。此外,我们还发现,至少一个参与 miRNA 生物发生的基因出现变异与转移之间存在统计学意义上的显著关联(p:0.02):总之,关键 miRNA 生物发生基因的基因组失调可能是表皮生长因子受体野生型肿瘤患者对治疗药物反应不同和发生转移的原因之一。
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Variant Analysis of miRNA Regulatory Genes in 35 Sporadic Lung Carcinoma Tumors

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.

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来源期刊
Doklady Biochemistry and Biophysics
Doklady Biochemistry and Biophysics 生物-生化与分子生物学
CiteScore
1.60
自引率
12.50%
发文量
68
审稿时长
6-12 weeks
期刊介绍: Doklady Biochemistry and Biophysics is a journal consisting of English translations of articles published in Russian in biochemistry and biophysics sections of the Russian-language journal Doklady Akademii Nauk. The journal''s goal is to publish the most significant new research in biochemistry and biophysics carried out in Russia today or in collaboration with Russian authors. The journal accepts only articles in the Russian language that are submitted or recommended by acting Russian or foreign members of the Russian Academy of Sciences. The journal does not accept direct submissions in English.
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