晚期肺癌的药物遗传学：功能性遗传多态性 AGXT Pro11Leu 对临床结局的预测价值？

Pharmacogenetics of advanced lung cancer: Predictive value of functional genetic polymorphism AGXT Pro11Leu in clinical outcome?

机构信息

i3S, Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; Tumour & Microenvironment Interactions Group, INEB, Biomedical Engineering Institute, University of Porto, Portugal; Department of Pulmonology, University Hospital of Coimbra, Portugal; Faculty of Medicine, University of Porto, Portugal; Molecular Oncology and Viral Pathology Group - Research Centre, Portuguese Institute of Oncology, Porto, Portugal.

Department of Clinical Pathology, University Hospital of Coimbra, Portugal.

出版信息

Pulmonology. 2021 Mar-Apr;27(2):116-123. doi: 10.1016/j.pulmoe.2020.11.007. Epub 2021 Jan 3.

DOI:10.1016/j.pulmoe.2020.11.007

PMID:33408043

Abstract

INTRODUCTION

AGXT gene codes for the enzyme alanine glyoxylate aminotransferase, which is involved in hepatic peroxisomal metabolism of platinum-based chemotherapeutic agents. The association of genetic variant AGXT rs34116584 on the clinical outcome and response to chemotherapy of patients with non-small cell lung cancer (NSCLC) remains to be established. Our aim was to evaluate the association of functional AGXT gene polymorphism in NSCLC progression, considering as primary and secondary endpoint, progression free survival (PFS) and overall survival (OS), respectively.

METHODS

Genotyping of theAGXT rs34116584 genetic polymorphism was performed by mass spectrometry on 168 DNA samples from patients with NSCLC (stages IIIA-IVB). Univariate survival analysis included the study of Kaplan-Meier curves with the Log-Rank test, while Cox regression was used as a multivariate analysis.

RESULTS

Multivariate analysis showed shorter PFS for T carriers [HR=2.0, 95% CI, 1.4-3.0, p<0.0001] and shorter OS [HR=1.8, 95% CI, 1.1-3.0, p=0.017] globally, as well as in a subgroup of patients (n=144) treated with first line platinum-based chemotherapy [HR=2.0, 95% CI, 1.3-3.1, p=0.001] and [HR=1.8, 95% CI, 1.1-3.1, p=0.026], respectively.

CONCLUSION

This polymorphism seems to have an impact on NSCLC progression, opening new perspectives for its inclusion as a pharmacogenetic predictor of response to platinum-based chemotherapy.

摘要

介绍

AGXT 基因编码的酶丙氨酸-乙醛酸氨基转移酶，参与肝脏过氧化物酶体中铂类化疗药物的代谢。遗传变异 AGXT rs34116584 与非小细胞肺癌（NSCLC）患者的临床结局和化疗反应的关系尚待确定。我们的目的是评估 AGXT 基因多态性与 NSCLC 进展的关系，分别将无进展生存期（PFS）和总生存期（OS）作为主要和次要终点。

方法

对 168 例 NSCLC 患者（IIIa-IVb 期）的 DNA 样本进行了 AGXT rs34116584 基因多态性的基因分型，采用质谱法。单变量生存分析包括 Kaplan-Meier 曲线的研究和对数秩检验，而 Cox 回归用于多变量分析。

结果

多变量分析显示，T 携带者的 PFS 更短[HR=2.0，95%CI，1.4-3.0，p<0.0001]，OS 更短[HR=1.8，95%CI，1.1-3.0，p=0.017]，这在全球范围内以及接受一线铂类化疗的患者亚组中[n=144，HR=2.0，95%CI，1.3-3.1，p=0.001]和[HR=1.8，95%CI，1.1-3.1，p=0.026]中均如此。