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Genome-Wide Transcriptional Analysis Reveals Alternative Splicing Event Profiles in Hepatocellular Carcinoma and Their Prognostic Significance.

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机构: [1]Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, China [2]North Sichuan Medical College, Institute of Hepato-Biliary-Pancreatic-Intestinal Disease, Nanchong, China [3]Department of Breast Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China [4]Department of Gastrointestinal Surgery, Nanchong Central Hospital, Nanchong, China [5]Department of Gastrointestinal Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
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关键词: alternative splicing genome-wide hepatocellular carcinoma prognosis RNA-seq

摘要:
Accumulating evidence indicates an unexpected role of aberrant splicing in hepatocellular carcinoma (HCC) that has been seriously neglected in previous studies. There is a need for a detailed analysis of alternative splicing (AS) and its underlying biological and clinical relevance in HCC. In this study, clinical information and corresponding RNA sequencing data of HCC patients were obtained from The Cancer Genome Atlas. Percent spliced in (PSI) values and transcriptional splicing patterns of genes were determined from the original RNA sequencing data using SpliceSeq. Then, based on the PSI values of AS events in different patients, a series of bioinformatics methods was used to identify differentially expressed AS events (DEAS), determine potential regulatory relationships, and investigate the correlation between DEAS and the patients' clinicopathological features. Finally, 25,934 AS events originating from 8,795 genes were screened with high reliability; 263 of these AS events were identified as DEAS. The parent genes of these DEAS formed an intricate network with roles in the regulation of cancer-related pathway and liver metabolism. In HCC, 36 splicing factors were involved in the dysregulation of part DEAS, 100 DEAS events were correlated with overall survival, and 71 DEAS events were correlated with disease-free survival. Stratifying HCC patients according to DEAS resulted in four clusters with different survival patterns. Significant variations in AS occurred during HCC initiation and maintenance; these are likely to be vital both for biological processes and in prognosis. The HCC-related AS events identified here and the splicing networks constructed will be valuable in deciphering the underlying role of AS in HCC.

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出版当年[2020]版:
大类 | 3 区 生物学
小类 | 3 区 遗传学
最新[2023]版:
大类 | 3 区 生物学
小类 | 3 区 遗传学
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出版当年[2020]版:
Q2 GENETICS & HEREDITY
最新[2023]版:
Q2 GENETICS & HEREDITY

影响因子: 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

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第一作者机构: [1]Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, China [2]North Sichuan Medical College, Institute of Hepato-Biliary-Pancreatic-Intestinal Disease, Nanchong, China
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通讯作者:
通讯机构: [1]Department of Hepatobiliary Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, China [2]North Sichuan Medical College, Institute of Hepato-Biliary-Pancreatic-Intestinal Disease, Nanchong, China
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