KITLG 的高表达是激活 A 型和 AB 型胸腺瘤中 MAPK 通路的新标志。
High expression of KITLG is a new hallmark activating the MAPK pathway in type A and AB thymoma.
机构信息
Department of Cardiothoracic Surgery, Tianjin Medical University General Hospital, Tianjin, China.
出版信息
Thorac Cancer. 2020 Jul;11(7):1944-1954. doi: 10.1111/1759-7714.13486. Epub 2020 May 28.
BACKGROUND
KIT proto-oncogene ligand (KITLG) is a pleiotropic factor which is found in diverse cancers and is involved in cell proliferation, differentiation, and survival. However, the value of KITLG in thymoma remains unclear.
METHODS
A total of 121 thymoma samples from The Cancer Genome Atlas Thymoma (TCGA-THYM) dataset were used to analyze KITLG related genome-wide expression profiles, and microRNA profiles and methylation alterations and a GEO dataset-GSE29695, including 37 samples was used as verification. For cell-based studies, specific small interfering RNA targeting KITLG or a KITLG overexpression vector were used to clarify the changes of the MAPK pathway in an AB thymoma cell line Thy0517.
RESULTS
Both datasets showed that high expression of KITLG was significantly associated with type A and AB thymoma. Through multiomic analysis of the TCGA-THYM, it was found that with the high expression of KITLG, there were 220 upregulated and 72 downregulated genes at the mRNA level, 79 positive and 78 negative miRNAs, 28 hypermethylation and 163 hypomethylation regions. In the thymoma cell line Thy0517, it was found that the expression of GRB2 and the phosphorylation levels of BRAF, MEK1/2, and ERK1/2 in the MAPK pathway were positively correlated with the change in KITLG.
CONCLUSIONS
High expression of KITLG is a new hallmark of WHO type A and AB thymomas in which it might play a critical role through the activation of the MAPK signaling pathway. Additionally, it is hoped that KITLG will become a potential target for the diagnosis of type A and AB thymoma through further research in the future.
KEY POINTS
SIGNIFICANT FINDINGS OF THE STUDY: KIT proto-oncogene ligand (KITLG) is a new hallmark of type A and AB thymomas which induce a series of aberrant alteration of mRNA, miRNA and DNA methylation. The expression of KITLG is significantly higher in type A and AB than other subtypes of thymoma.
WHAT THIS STUDY ADDS
KITLG activated the MAPK signaling pathway to promote type A and AB thymoma which might be a potential diagnostic biomarker or target.
背景
KIT 原癌基因配体（KITLG）是一种多效因子，存在于多种癌症中，参与细胞增殖、分化和存活。然而，KITLG 在胸腺瘤中的价值尚不清楚。
方法
使用来自癌症基因组图谱胸腺瘤（TCGA-THYM）数据集的 121 例胸腺瘤样本分析 KITLG 相关的全基因组表达谱、microRNA 谱和甲基化改变，使用 GEO 数据集-GSE29695（包括 37 例样本）进行验证。对于细胞基础研究，使用针对 KITLG 的特定小干扰 RNA 或 KITLG 过表达载体，以阐明 MAPK 通路在 AB 胸腺瘤细胞系 Thy0517 中的变化。
结果
两个数据集均显示 KITLG 高表达与 A 型和 AB 型胸腺瘤显著相关。通过 TCGA-THYM 的多组学分析，发现随着 KITLG 的高表达，在 mRNA 水平上有 220 个上调基因和 72 个下调基因，79 个正相关和 78 个负相关 microRNA，28 个 hypermethylation 和 163 hypomethylation 区域。在胸腺瘤细胞系 Thy0517 中，发现 MAPK 通路中 GRB2 的表达和 BRAF、MEK1/2 和 ERK1/2 的磷酸化水平与 KITLG 的变化呈正相关。
结论
KITLG 的高表达是 WHO 型 A 和 AB 胸腺瘤的一个新标志，它可能通过激活 MAPK 信号通路发挥关键作用。此外，希望通过未来的进一步研究，KITLG 能够成为 A 型和 AB 胸腺瘤诊断的潜在靶点。
关键点
研究的重要发现：KIT 原癌基因配体（KITLG）是 A 型和 AB 胸腺瘤的一个新标志，它诱导了一系列异常的 mRNA、miRNA 和 DNA 甲基化改变。KITLG 在 A 型和 AB 型胸腺瘤中的表达明显高于其他亚型。
本研究的新增内容：KITLG 激活 MAPK 信号通路促进 A 型和 AB 胸腺瘤，可能成为潜在的诊断生物标志物或靶标。
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