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Prognostic alternative mRNA splicing signature in hepatocellular carcinoma: a study based on large-scale sequencing data.

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机构： [1]Liver Cancer Institute, Zhongshan Hospital,Fudan University, Shanghai200032, China [2]State Key Laboratory of Genetic Engineering, Fudan University, Shanghai200032, China, [3]Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministryof Health, Renji Hospital, School of Medicine, Shanghai Institute of Digestive Disease, Shanghai Jiao Tong University,,Shanghai, China, [4]Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China, [5]Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China [6]Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China

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Most genes are alternatively spliced and increasing number of evidences show that alternative splicing (AS) is modified and related to tumor progression. Systematic profiles of AS signature in hepatocellular carcinoma (HCC) is absent and urgently needed. Here, differentially spliced AS transcripts between HCC and non-HCC tissues were compared, prognosis-associated AS events by using univariate Cox regression analysis were selected. Our gene functional enrichment analysis demonstrated the potential pathways enriched by survival-associated AS. Prognostic AS signatures were then constructed for HCC prognosis prediction by Lasso regression model. We also analyzed splicing factors (SFs) regulating underlying mechanisms by Pearson correlation and then built corresponding regulatory networks. In addition, we explored the performance of AS signature in the mutated HCC samples. Genome-wide AS events in 377 HCC patients from TCGA were profiled. Among 34 163 AS events in 8985 genes, 3950 AS events in 2403 genes associated with overall survival (OS) significantly for HCC were detected. In addition, computational algorithm results showed that metabolic and ribosome pathways may be the potential molecular mechanisms regulating the poor prognosis. More importantly, survival-associated AS signatures revealed high performance in predicting HCC prognosis. The area under curve for AS signature was 0.806 in all HCC and 0.944 in TP53 mutated HCC samples at 2000 days of OS. We submitted prognostic SFs to build the AS regulatory network, from which we found prognostic AS events were significantly enriched in metabolism-related pathways. A robust AS signature for HCC patients and revealed the regulatory splicing networks contributing to the potential significantly enriched metabolism-related pathways. © The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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出版当年[2019]版：

大类 | 2 区医学

小类 | 3 区肿瘤学

最新[2023]版：

大类 | 3 区医学

小类 | 3 区肿瘤学

第一作者：

第一作者机构： [1]Liver Cancer Institute, Zhongshan Hospital,Fudan University, Shanghai200032, China [2]State Key Laboratory of Genetic Engineering, Fudan University, Shanghai200032, China,

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通讯机构： [1]Liver Cancer Institute, Zhongshan Hospital,Fudan University, Shanghai200032, China [2]State Key Laboratory of Genetic Engineering, Fudan University, Shanghai200032, China,

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