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pmid:32463597
High expression of KITLG is a new hallmark activating the MAPK pathway in type A and AB thymoma.
Zhaoyu Yang · Shinan Liu · Yuanguo Wang · Yuan Chen · Peng Zhang · Yimei Liu · Hui Zhang · Peng Zhang · Ziyou Tao · Kai Xiong
Thoracic cancer · 2020 doi:10.1111/1759-7714.13486
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Complete file
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However, the value of KITLG in thymoma remains unclear.\nMETHODS: 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.\nRESULTS: 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.\nCONCLUSIONS: 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.\nKEY 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.\nWHAT 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.", "claims": [{"id": "claim-method", "statement": "Student's t‐test and multiple hypothesis correction were used to identify genome‐wide differences in gene, miRNA, and methylation profiles between the KITLGhigh and KITLGlow groups. All analyses were performed using the R limma software package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32463597", "locator": "sections[10] \"Statistical analysis\" paragraph 2", "quote": "Student's t‐test and multiple hypothesis correction were used to identify genome‐wide differences in gene, miRNA, and methylation profiles between the KITLGhigh and KITLGlow groups. 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