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宫颈鳞状细胞癌中预后可变剪接标志物。

Prognostic alternative splicing signature in cervical squamous cell carcinoma.

机构信息

Department of Cell Biology and Genetics, School of Pre-clinical Medicine, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.

Department of Pathophysiology, School of Pre-clinical Medicine, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.

出版信息

IET Syst Biol. 2020 Dec;14(6):314-322. doi: 10.1049/iet-syb.2019.0095.

Abstract

Basing on alternative splicing events (ASEs) databases, the authors herein aim to explore potential prognostic biomarkers for cervical squamous cell carcinoma (CESC). mRNA expression profiles and relevant clinical data of 223 patients with CESC were obtained from The Cancer Genome Atlas (TCGA). Correlated genes, ASEs and percent-splice-in (PSI) were downloaded from SpliceSeq, respectively. The PSI values of survival-associated alternative splicing events (SASEs) were used to construct the basis of a prognostic index (PI). A protein-protein interaction (PPI) network of genes related to SASEs was generated by STRING and analysed with Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Consequently, 41,776 ASEs were discovered in 19,724 genes, 2596 of which linked with 3669 SASEs. The PPI network of SASEs related genes revealed that TP53 and UBA52 were core genes. The low-risk group had a longer survival period than high-risk counterparts, both groups being defined according to PI constructed upon the top 20 splicing events or PI on the overall splicing events. The AUC value of ROC reached up to 0.88, demonstrating the prognostic potential of PI in CESC. These findings suggested that ASEs involve in the pathogenesis of CESC and may serve as promising prognostic biomarkers for this female malignancy.

摘要

基于剪接事件(ASEs)数据库,作者旨在探索宫颈癌(CESC)的潜在预后生物标志物。从癌症基因组图谱(TCGA)获得了 223 名 CESC 患者的 mRNA 表达谱和相关临床数据。从 SpliceSeq 分别下载了相关基因、ASE 和百分比剪接(PSI)。使用与生存相关的剪接事件(SASEs)的 PSI 值来构建预后指数(PI)的基础。通过 STRING 生成与 SASEs 相关的基因的蛋白质-蛋白质相互作用(PPI)网络,并通过基因本体论(GO)和京都基因与基因组百科全书(KEGG)进行分析。结果发现,在 19724 个基因中发现了 41776 个 ASE,其中 2596 个与 3669 个 SASE 相关。SASE 相关基因的 PPI 网络表明,TP53 和 UBA52 是核心基因。根据基于前 20 个剪接事件或整体剪接事件的 PI 定义的低风险组比高风险组具有更长的生存期。ROC 的 AUC 值高达 0.88,表明 PI 在 CESC 中的预后潜力。这些发现表明 ASEs 参与了 CESC 的发病机制,可能是这种女性恶性肿瘤有前途的预后生物标志物。

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