拷贝数变化
生物
癌症研究
DNA甲基化
癌变
奥拉帕尼
基因
替莫唑胺
分子生物学
遗传学
基因表达
基因组
聚合酶
聚ADP核糖聚合酶
胶质母细胞瘤
作者
Xiaoshuai Wang,Yinuo Han,Jia Li,Dong-Chun Hong,Zi Xue,Hao Huang,ZeFeng Du,Yingdong Hou,Hongbo Li,Hongyi Li,Hongyi Liao,Xianbiao Xie,Changhai Ding
出处
期刊:Life Sciences
[Elsevier]
日期:2021-01-01
卷期号:265: 118734-118734
被引量:17
标识
DOI:10.1016/j.lfs.2020.118734
摘要
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. 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. 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. 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.
科研通智能强力驱动
Strongly Powered by AbleSci AI