Integrative analysis reveals the prognostic value and functions of splicing factors implicated in hepatocellular carcinoma.
Integrative analysis reveals the prognostic value and functions of splicing factors implicated in hepatocellular carcinoma.
复制标题
DOI：
10.1038/s41598-021-94701-8
复制
发表时间：
2021-07-26
影响因子：
4.6
通讯作者：
Yang Q
中科院分区：
文献类型：
--
作者：
Wang Y;Yang F;Shang J;He H;Yang Q
剪接因子（SFs）通过调节肿瘤相关的选择性剪接（AS）事件，在多种癌症的发病机制中发挥关键作用。然而，SFs在肝细胞癌（HCC）中的临床价值和生物学功能尚不清楚。在本研究中，我们在HCC中鉴定了40个失调的SFs，并建立了由4个SFs （DNAJC6、ZC3H13、IGF2BP3、DDX19B）组成的预后模型。结果表明，该预测模型具有较好的预测效率和独立性。基因集富集分析（GSEA）表明，我们的预后模型计算的风险评分与多种癌症相关途径和代谢过程显著相关。此外，我们构建了SFs-AS事件调控网络，并从中提取了108个蛋白编码基因，用于后续的功能探索。蛋白质-蛋白质相互作用（PPI）网络描述了这108个蛋白质编码基因之间潜在的相互作用。GO和KEGG通路分析研究了本体基因集和由这108个蛋白质编码基因富集的典型通路。与GSEA和KEGG的结果重叠，我们确定了7条通路是通过触发HCC中异常AS事件而受我们的预后模型调节的潜在通路。综上所述，本研究建立了一种有效的基于SFs的HCC患者预后模型。SFs及其相关AS事件的功能探索为探讨SFs在HCC肿瘤发生中的生物学功能和机制提供了方向。
Splicing factors (SFs) play critical roles in the pathogenesis of various cancers through regulating tumor-associated alternative splicing (AS) events. However, the clinical value and biological functions of SFs in hepatocellular carcinoma (HCC) remain obscure. In this study, we identified 40 dysregulated SFs in HCC and established a prognostic model composed of four SFs (DNAJC6, ZC3H13, IGF2BP3, DDX19B). The predictive efficiency and independence of the prognostic model were confirmed to be satisfactory. Gene Set Enrichment Analysis (GSEA) illustrated the risk score calculated by our prognostic model was significantly associated with multiple cancer-related pathways and metabolic processes. Furthermore, we constructed the SFs-AS events regulatory network and extracted 108 protein-coding genes from the network for following functional explorations. Protein–protein interaction (PPI) network delineated the potential interactions among these 108 protein-coding genes. GO and KEGG pathway analyses investigated ontology gene sets and canonical pathways enriched by these 108 protein-coding genes. Overlapping the results of GSEA and KEGG, seven pathways were identified to be potential pathways regulated by our prognostic model through triggering aberrant AS events in HCC. In conclusion, the present study established an effective prognostic model based on SFs for HCC patients. Functional explorations of SFs and SFs-associated AS events provided directions to explore biological functions and mechanisms of SFs in HCC tumorigenesis.
登录
查看更多内容
影响因子：
14.9
作者：
Kanehisa M;Furumichi M;Sato Y;Ishiguro-Watanabe M;Tanabe M
通讯作者：
Tanabe M
影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
DOI：
10.1093/bioinformatics/bts452
发表时间：
2012-09-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Ryan MC;Cleland J;Kim R;Wong WC;Weinstein JN
通讯作者：
Weinstein JN
昼夜节律调节剂 HLF 的下调通过 PPAR/NF-κ b 信号传导促进非小细胞肺癌的多器官远处转移
影响因子：
9.7
作者：
Chen, Jiarong;Liu, Aibin;Huang, Yanming
通讯作者：
Huang, Yanming
DOI：
10.1007/978-0-387-77374-2_8
发表时间：
2007-01-01
期刊：
ALTERNATIVE SPLICING IN THE POSTGENOMIC ERA
影响因子：
--
作者：
Martinez-Contreras, Rebeca;Cloutier, Philippe;Chabot, Benoit
通讯作者：
Chabot, Benoit