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ABCG2基因rs2231142(421C>A)变异对吉非替尼治疗的EGFR突变型非小细胞肺癌患者临床结局的影响:一项综合荟萃分析。

Impact of ABCG2 rs2231142(421C>A) Variant on the Clinical Outcomes of Patients With -mutated Non-small Cell Lung Cancer Treated With Gefitinib: A Comprehensive Meta-analysis.

作者信息

DE Moraes Francisco Cezar Aquino, Souza Maria Eduarda Cavalcanti, DA Silva Emanuele Rocha, Kreuz Michele, Burbano Rommel Mario Rodriguez

机构信息

Federal University of Pará, Belém, Pará, Brazil;

University of Pernambuco, Recife, Pernambuco, Brazil.

出版信息

Anticancer Res. 2024 Dec;44(12):5361-5370. doi: 10.21873/anticanres.17363.

Abstract

BACKGROUND/AIM: Lung cancer accounts for the largest percentage of cancer deaths worldwide, with non-small cell lung cancer (NSCLC) being the predominant type. Gefitinib, an EGFR tyrosine kinase inhibitor (EGFR-TKI), has shown marked efficacy in NSCLC patients with an EGFR mutation. However, gefitinib resistance because of ABCG2 polymorphisms such as rs2231142(421C > A) might limit its clinical use.

PATIENTS AND METHODS

This meta-analysis followed the PRISMA guidelines and investigated the impact of the ABCG2 rs2231142 variant on gefitinib treatment outcomes in patients with NSCLC, using the PECOS model for study selection.

RESULTS

A total of 585 NSCLC patients treated with gefitinib were assessed for the association between genetic variants of the ABC transporter genes, specifically the ABCG2 C421A polymorphism, and clinical outcomes. No association was found between the ABCG2 C421A polymorphism and response to gefitinib chemotherapy (p=0.653; I2=0%). Similarly, no correlation was observed with gefitinib-induced skin rash (p=0.161177; I=0%), diarrhea (p=0.064441), hepatotoxicity (p=0.210916; I=0%), or interstitial pneumonia (p=0.138937).

CONCLUSION

The ABCG2 rs2231142 polymorphism plays a significant role in the clinical outcomes of patients with EGFR-mutated NSCLC treated with gefitinib, warranting further investigation to clarify its impact on treatment efficacy and patient safety.

摘要

背景/目的:肺癌是全球癌症死亡占比最大的疾病,其中非小细胞肺癌(NSCLC)是主要类型。吉非替尼是一种表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKI),对具有EGFR突变的NSCLC患者显示出显著疗效。然而,由ABCG2基因多态性如rs2231142(421C>A)导致的吉非替尼耐药可能会限制其临床应用。

患者与方法

本荟萃分析遵循PRISMA指南,采用PECOS模型进行研究选择,调查ABCG2 rs2231142变异对NSCLC患者吉非替尼治疗结果的影响。

结果

共评估了585例接受吉非替尼治疗的NSCLC患者,以确定ABC转运蛋白基因的遗传变异,特别是ABCG2 C421A多态性与临床结果之间的关联。未发现ABCG2 C421A多态性与吉非替尼化疗反应之间存在关联(p=0.653;I2=0%)。同样,未观察到与吉非替尼引起的皮疹(p=0.161177;I=0%)、腹泻(p=0.064441)、肝毒性(p=0.210916;I=0%)或间质性肺炎(p=0.138937)存在相关性。

结论

ABCG2 rs2231142多态性在接受吉非替尼治疗的EGFR突变NSCLC患者的临床结果中起重要作用,需要进一步研究以阐明其对治疗疗效和患者安全性的影响。

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