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评估 CCR7/CCL19 轴与非小细胞肺癌中选定的调节 miRNA 之间的关系。

An assessment of the relationship between the expression of CCR7/CCL19 axis and selected regulatory miRNAs in non-small cell lung cancer.

机构信息

Department of Biomedicine and Genetics, Chair of Biology and Medical Parasitology, Medical University of Lodz, Lodz, Poland.

Department of Thoracic, General and Oncological Surgery, Medical University of Lodz, Lodz, Poland.

出版信息

Mol Biol Rep. 2019 Oct;46(5):5389-5396. doi: 10.1007/s11033-019-04993-3. Epub 2019 Aug 28.

Abstract

CC chemokine receptor type 7 (CCR7) and its ligands has been implicated in the occurrence and progression of NSCLC. Previous studies have revealed that the diagnostic value of CCR7/CCL19 axis in lung tumorigenesis remains controversial. The present study evaluates the relationship between the mRNA expression of CCR7/CCL19 axis and selected regulatory miRNAs in NSCLC patients. It analyzes the expression level of CCR7 mRNA and its ligand in tumor tissue in relation to expression level of two miRNAs: miR let-7a and miR-335, as transcriptional regulators of study genes. Twenty-seven patients (n = 27) were enrolled. The expression of the studied genes and miRNAs was evaluated by qPCR. Tumour tissue fragments, adjacent macroscopically-unchanged lung tissue (control) and patient serum were used as biological material for study. Elevated expression of CCR7 and CCL19 mRNA was observed in patients with metastasis to lymph nodes. We noticed upregulated miR-335 expression and downregulated miR let-7a expression in patient serum with regard to AJCC tumor staging. Higher miR-335 expression and lower miR let-7a expression level was observed in patients with metastasis to lymph node. The presence of changes observed in the expression level of miR-335 and miR let-7a in the serum of NSCLC patients in relation to lymph node metastases and tumor stage may serve as a non-invasive molecular biomarker of tumor progression; however, this observation requires further investigation.

摘要

CC 趋化因子受体 7 (CCR7) 及其配体与 NSCLC 的发生和进展有关。先前的研究表明,CCR7/CCL19 轴在肺肿瘤发生中的诊断价值仍存在争议。本研究评估了 CCR7/CCL19 轴的 mRNA 表达与 NSCLC 患者中选定的调节 miRNA 之间的关系。分析了肿瘤组织中 CCR7 mRNA 及其配体的表达水平与两种 miRNA(miR let-7a 和 miR-335)的表达水平之间的关系,这两种 miRNA 是研究基因的转录调节剂。共纳入 27 名患者(n=27)。通过 qPCR 评估研究基因和 miRNA 的表达。肿瘤组织片段、相邻宏观无变化的肺组织(对照)和患者血清被用作研究的生物材料。在发生淋巴结转移的患者中观察到 CCR7 和 CCL19 mRNA 的表达升高。我们注意到,根据 AJCC 肿瘤分期,患者血清中 miR-335 的表达上调,miR let-7a 的表达下调。在发生淋巴结转移的患者中,miR-335 的表达较高,miR let-7a 的表达水平较低。在与淋巴结转移和肿瘤分期相关的 NSCLC 患者血清中观察到 miR-335 和 miR let-7a 表达水平的变化,可能作为肿瘤进展的非侵入性分子生物标志物;然而,这一观察结果需要进一步研究。

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