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黑色素瘤中与预后相关的 RNA 可变剪接信号的系统分析。

Systemic Analysis of the Prognosis-Related RNA Alternative Splicing Signals in Melanoma.

机构信息

Department of Plastic Surgery, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China (mainland).

Department of Gynecology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China (mainland).

出版信息

Med Sci Monit. 2020 Mar 21;26:e921133. doi: 10.12659/MSM.921133.

Abstract

BACKGROUND Alternative splicing (AS), the mechanism underlying the occurrence of protein diversity, may result in cancer genesis and development when it becomes out of control, as suggested by a growing number of studies. However, systemically analyze of AS events at the genome-wide level for skin cutaneous melanoma (SKCM) is still in a preliminary phase. This study aimed to systemically analyze the bioinformatics of the AS events at a genome-wide level using The Cancer Genome Atlas (TCGA) SKCM data. MATERIAL AND METHODS The SpliceSeq tool was used to analyze the AS profiles for SKCM clinical specimens from the TCGA database. The association between AS events and overall survival was analyzed by Cox regression analysis. AS event intersections and a gene interaction network were established by UpSet plot. A multivariate survival model was used to establish a feature genes prognosis model. RESULTS A total of 103 SKCM patients with full clinical parameters available were included in this study. We established an AS network that investigated the relationship between AS events and clinical prognosis information. Furthermore, 4 underlying feature genes of SKCM (MCF2L, HARS, TFR2, and RALGPS1) were found in the AS network. We performed function analysis as well as correlation analysis of AS events with gene expression. Using the multivariate survival model, we further confirmed the 4 genes that impacted the classifying SKCM prognosis at the level of AS events as well as gene expression, especially in wild-type SKCM. CONCLUSIONS AS events could be ideal indicators for SKCM prognosis. The key feature gene MCF2L played an important role in wild-type SKCM.

摘要

背景

越来越多的研究表明,可变剪接(AS)是产生蛋白质多样性的机制,当它失去控制时,可能导致癌症的发生和发展。然而,在全基因组水平上系统地分析皮肤黑色素瘤(SKCM)中的 AS 事件仍处于初步阶段。本研究旨在使用癌症基因组图谱(TCGA)SKCM 数据,在全基因组水平上系统地分析 AS 事件的生物信息学。

材料和方法

使用 SpliceSeq 工具分析 TCGA 数据库中 SKCM 临床标本的 AS 谱。通过 Cox 回归分析,分析 AS 事件与总生存期之间的关系。通过 Upset 图建立 AS 事件的交集和基因相互作用网络。使用多变量生存模型建立特征基因预后模型。

结果

本研究共纳入 103 例具有完整临床参数的 SKCM 患者。我们建立了一个 AS 网络,研究了 AS 事件与临床预后信息之间的关系。此外,在 AS 网络中发现了 SKCM 的 4 个潜在特征基因(MCF2L、HARS、TFR2 和 RALGPS1)。我们对 AS 事件与基因表达的功能分析和相关性分析。使用多变量生存模型,我们进一步证实了 4 个基因在 AS 事件和基因表达水平上影响 SKCM 预后的分类,特别是在野生型 SKCM 中。

结论

AS 事件可以作为 SKCM 预后的理想指标。关键特征基因 MCF2L 在野生型 SKCM 中发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9bf0/7111138/ecdeefecf64d/medscimonit-26-e921133-g001.jpg

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