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Multi-omics analysis of copy number variations of RNA regulatory genes in soft tissue sarcoma

Wang, X, Han, Y, Li, J, Hong, D, Xue, Z, Huang, H, Du, Z, Hou, Y, Li, H, Li, H, Liao, H, Xie, X and Ding, C ORCID: 0000-0002-9479-730X 2020 , 'Multi-omics analysis of copy number variations of RNA regulatory genes in soft tissue sarcoma' , Life Sciences , pp. 1-12 , doi: 10.1016/j.lfs.2020.118734.

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Aims: RNA regulatory genes were closely associated with tumorigenesis and prognosis in multiple tumors. Copy number variation (CNV) is a frequent characteristic in soft tissue sarcomas (STS). However, little is known regarding their possible roles in STS.Main methods: RNA sequence profiles and CNV data of 255 STS patients were downloaded from the Cancer Genome Atlas (TCGA). The correlation analysis involved CNVs of RNA regulatory genes, patient survival, immune infiltration, and DNA methylation. Drug sensitivity (IC50) was analyzed and validated by MTT assays in STS cell lines.Key findings: CNV events were frequently observed in all kinds (m6A, m5C, ac4C, m1A, m3C, m6Am, m7G, and Ψ) of RNA regulatory genes. Diploid copy number (CN) of METTL4 was associated with better overall survival (OS) in STS and the subtypes (leiomyosarcoma, LMS; dedifferentiated liposarcoma, DDLPS). In STS and LMS, diploid CN of METTL4 was significantly associated with higher infiltration fraction of resting mast cells. In STS and DDLPS, diploid CN of METTL4 possessed lower methylation level in CpG site of cg12105018, which represented better OS. Besides, sensitive drugs for STS cell lines were analyzed according to lower IC50 for the loss CN of METTL4. Temozolomide and Olaparib were identified. Further validation by MTT assays demonstrated that GCT was the most sensitive cell line to both Temozolomide and Olaparib.Significance: CNV of METTL4 could be a prognostic biomarker for STS by potentially influencing mast cell infiltration and DNA methylation. Besides, STS with loss CN of METTL4 would be sensitive to Temozolomide and Olaparib.

Item Type: Article
Authors/Creators:Wang, X and Han, Y and Li, J and Hong, D and Xue, Z and Huang, H and Du, Z and Hou, Y and Li, H and Li, H and Liao, H and Xie, X and Ding, C
Keywords: copy number variation, DNA methylation, post-transcriptional RNA modification, soft tissue sarcoma, tumor microenvironment
Journal or Publication Title: Life Sciences
Publisher: Pergamon-Elsevier Science Ltd
ISSN: 0024-3205
DOI / ID Number: 10.1016/j.lfs.2020.118734
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Copyright 2020 Elsevier Inc.

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