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ABCB1 基因多态性及其表达对非小细胞肺癌发生、发展及治疗的影响——初步报告。

The impact of ABCB1 gene polymorphism and its expression on non-small-cell lung cancer development, progression and therapy - preliminary report.

机构信息

Laboratory of Molecular Diagnostics and Pharmacogenomics, Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Medical University of Lodz, ul. Muszynskiego 1, 90-151, Lodz, Poland.

Department of Thoracic Surgery, Memorial Copernicus Hospital, Medical University of Lodz, Lodz, Poland.

出版信息

Sci Rep. 2020 Apr 10;10(1):6188. doi: 10.1038/s41598-020-63265-4.

DOI:10.1038/s41598-020-63265-4
PMID:32277145
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7148348/
Abstract

The ABCB1 gene belongs to ATP binding cassette (ABC) transporter genes that has been previously implicated in cancer progression and drug response. This study aimed to evaluate the association between the SNP 3435 and the expression of the ABCB1 gene in lung cancer patients in the Polish population in comparison to clinicopathological parameters and treatment. 150 RNA and 47 DNA samples were isolated from 49 lung cancer cases including both tissue samples and blood taken from the same patients at three time points: diagnosis, 100 days and one year after the surgical intervention. Qualitative and real-time PCR analysis of expression were done, also genotyping by PCR-RFLP. Mutant homozygous TT and allele T are present statistically significantly more frequently in the group of patients with lung cancer. There is no difference with expression level in lung cancer tissue and blood sample taken from the same patients before surgical treatment. On the basis of blood samples analysis it was observed that the expression level of ABCB1 mRNA was growing in time. Higher levels were marked after 100 days and one year after the surgical intervention. The complementary pharmacological treatment induced higher expression levels of ABCB1. The presented data suggest an important role of ABCB1 in lung cancer, the increasing level of ABCB1 mRNA which can be connected with induction of multidrug resistance mechanism is also significant, that observation must be confirmed in further analysis.

摘要

ABCB1 基因属于 ATP 结合盒(ABC)转运体基因,先前已被证实与癌症的进展和药物反应有关。本研究旨在评估 SNP3435 与波兰人群肺癌患者 ABCB1 基因表达之间的关联,并与临床病理参数和治疗进行比较。从 49 例肺癌病例中分离出 150 份 RNA 和 47 份 DNA 样本,包括组织样本和来自同一患者的血液样本,分别在三个时间点采集:诊断时、手术干预后 100 天和一年。进行了表达的定性和实时 PCR 分析,还通过 PCR-RFLP 进行了基因分型。在肺癌患者组中,突变纯合子 TT 和等位基因 T 存在统计学意义上的更高频率。在手术治疗前从同一患者采集的肺癌组织和血液样本的表达水平没有差异。基于血液样本分析,观察到 ABCB1mRNA 的表达水平随时间增长。在手术干预后 100 天和一年后标记出更高的水平。互补的药物治疗诱导了更高的 ABCB1 表达水平。所呈现的数据表明 ABCB1 在肺癌中具有重要作用,与多药耐药机制诱导相关的 ABCB1mRNA 水平的增加也具有重要意义,这一观察结果必须在进一步的分析中得到证实。

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