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评估非小细胞肺癌患者中 IL-17A 基因表达水平与调节 miRNA-9 之间的关系与肿瘤进展的关系:一项初步研究。

Evaluation of the relationship between the IL-17A gene expression level and regulatory miRNA-9 in relation to tumor progression in patients with non-small cell lung cancer: a pilot study.

机构信息

Department of Biomedicine and Genetics, Medical University of Lodz, Poland St. 251, C-5, 92-213, Lodz, Poland.

Clinic of Thoracic Surgery, General and Oncological Surgery University Clinical Hospital named after the Military Medical Academy - Central Veterans' Hospital, Medical University of Lodz, Poland St. Żeromskiego 113, 90-549, Lodz, Poland.

出版信息

Mol Biol Rep. 2020 Jan;47(1):583-592. doi: 10.1007/s11033-019-05164-0. Epub 2019 Nov 9.

DOI:10.1007/s11033-019-05164-0
PMID:31707599
Abstract

A pro-inflammatory cytokine, IL-17A, is associated with increased risk of developing numerous cancers, including non-small cell lung cancer (NSCLC). IL-17A is a target gene for miR-9. This encouraged us to analyze these two genes in terms of their usefulness as prognostic markers in NSCLC. The expression levels of IL-17A gene and miR-9 was assessed in 26 NSCLC tissue samples and 26 unchanged lung tissue adjacent to lung tumors (control tissue), using qPCR. In both tissue groups, a decreased expression of IL-17A was observed in 100% of samples. Increased expression of miRNA-9 was observed in 92% of tumor samples, and in 100% of control samples. Neither statistical differences in the level of expression IL-17A depending on the patient's age, gender, smoking status, nor histopathology of the cancer was found. Regarding the presence of nodule metastasis ('N' value in TNM classification), significantly lower expression level of IL-17A was observed in cN2 as compared with cN1 group. Additionally, statistically lower IL-17A expression was found in III versus II tumor stage (cAJCC classification). Significant negative correlation between both studied genes was revealed in SCC subgroup. This leads to the conclusion that miRNA-9 can regulate the expression of IL-17A as an IL-17A mRNA antagonistic mediator. Inhibition of proinflammatory action of IL-17A in correlation with tumor progression can be related to various activity of Th17 cells on cancer development according to its immunogenicity, and also may suggest suppressive role of IL-17A in tumor progression. However, because of low number of analyzed samples, further studies on the functional role of IL-17A in development and/or progression NSCLC seem warranted.

摘要

一种促炎细胞因子,IL-17A,与多种癌症(包括非小细胞肺癌(NSCLC))的发展风险增加有关。IL-17A 是 miR-9 的靶基因。这鼓励我们分析这两个基因在 NSCLC 中的预后标记物的有用性。使用 qPCR 评估了 26 个 NSCLC 组织样本和 26 个与肺肿瘤相邻的未改变肺组织(对照组织)中 IL-17A 基因和 miR-9 的表达水平。在两组组织中,观察到 100%的样本中 IL-17A 的表达降低。在 92%的肿瘤样本和 100%的对照样本中观察到 miRNA-9 的表达增加。未发现 IL-17A 表达水平随患者年龄、性别、吸烟状况或癌症的组织病理学变化而变化的统计学差异。关于结节转移的存在(TNM 分类中的“N”值),与 cN1 组相比,cN2 组中 IL-17A 的表达水平显著降低。此外,在 III 期与 II 期肿瘤分期(cAJCC 分类)相比,IL-17A 的表达水平统计学降低。在 SCC 亚组中发现了两个研究基因之间存在显著的负相关。这得出结论,miRNA-9 可以作为 IL-17A mRNA 的拮抗调节剂来调节 IL-17A 的表达。与肿瘤进展相关的 IL-17A 的促炎作用的抑制可能与 Th17 细胞在癌症发展中的各种活性有关,根据其免疫原性,也可能提示 IL-17A 在肿瘤进展中的抑制作用。然而,由于分析样本数量较少,进一步研究 IL-17A 在 NSCLC 发展和/或进展中的功能作用似乎是必要的。

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