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Identification of prognostic and metastasis-related alternative splicing signatures in hepatocellular carcinoma
As the most common neoplasm in digestive system, hepatocellular carcinoma (HCC) is one of the most important leading cause of cancer deaths worldwide. Its high-frequency metastasis and relapse rate lead to the poor survival of HCC patients. However, the mechanism of HCC metastasis is still unclear....
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364508/ https://www.ncbi.nlm.nih.gov/pubmed/32627826 http://dx.doi.org/10.1042/BSR20201001 |
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author | Huang, Runzhi Yan, Gaili Sun, Hanlin Zhang, Jie Song, Dianwen Kong, Rui Yan, Penghui Hu, Peng Xie, Aiqing Wang, Siqiao Zhuang, Juanwei Yin, Huabin Meng, Tong Huang, Zongqiang |
author_facet | Huang, Runzhi Yan, Gaili Sun, Hanlin Zhang, Jie Song, Dianwen Kong, Rui Yan, Penghui Hu, Peng Xie, Aiqing Wang, Siqiao Zhuang, Juanwei Yin, Huabin Meng, Tong Huang, Zongqiang |
author_sort | Huang, Runzhi |
collection | PubMed |
description | As the most common neoplasm in digestive system, hepatocellular carcinoma (HCC) is one of the most important leading cause of cancer deaths worldwide. Its high-frequency metastasis and relapse rate lead to the poor survival of HCC patients. However, the mechanism of HCC metastasis is still unclear. Alternative splicing events (ASEs) have a great effect in cancer development, progression and metastasis. We downloaded RNA sequencing and seven types of ASEs data of HCC samples, in order to explore the mechanism of ASEs underlying tumorigenesis and metastasis of HCC. The data were taken from the The Cancer Genome Atlas (TCGA) and TCGASpliceSeq databases. Univariate Cox regression analysis was used to determine a total of 3197 overall survival-related ASEs (OS-SEs). And based on five OS-SEs screened by Lasso regression, we constructed a prediction model with the Area Under Curve of 0.765. With a good reliability of the model, the risk score was also proved to be an independent predictor. Among identified 390 candidate SFs, Y-box protein 3 (YBX3) was significantly correlated with OS and metastasis. Among 177 ASEs, ATP-binding cassette subfamily A member 6 (ABCA6)-43162-AT and PLIN5-46808-AT were identified both associated with OS, bone metastasis and co-expressed with SFs. Then we identified primary bile acid biosynthesis as survival-related (KEGG) pathway by Gene Set Variation Analysis (GSVA) and univariate regression analysis, which was correlated with ABCA6-43162-AT and PLIN5-46808-AT. Finally, we proposed that ABCA6-43162-AT and PLIN5-46808-AT may contribute to HCC poor prognosis and metastasis under the regulation of aberrant YBX3 through the pathway of primary bile acid biosynthesis. |
format | Online Article Text |
id | pubmed-7364508 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Portland Press Ltd. |
record_format | MEDLINE/PubMed |
spelling | pubmed-73645082020-07-27 Identification of prognostic and metastasis-related alternative splicing signatures in hepatocellular carcinoma Huang, Runzhi Yan, Gaili Sun, Hanlin Zhang, Jie Song, Dianwen Kong, Rui Yan, Penghui Hu, Peng Xie, Aiqing Wang, Siqiao Zhuang, Juanwei Yin, Huabin Meng, Tong Huang, Zongqiang Biosci Rep Bioinformatics As the most common neoplasm in digestive system, hepatocellular carcinoma (HCC) is one of the most important leading cause of cancer deaths worldwide. Its high-frequency metastasis and relapse rate lead to the poor survival of HCC patients. However, the mechanism of HCC metastasis is still unclear. Alternative splicing events (ASEs) have a great effect in cancer development, progression and metastasis. We downloaded RNA sequencing and seven types of ASEs data of HCC samples, in order to explore the mechanism of ASEs underlying tumorigenesis and metastasis of HCC. The data were taken from the The Cancer Genome Atlas (TCGA) and TCGASpliceSeq databases. Univariate Cox regression analysis was used to determine a total of 3197 overall survival-related ASEs (OS-SEs). And based on five OS-SEs screened by Lasso regression, we constructed a prediction model with the Area Under Curve of 0.765. With a good reliability of the model, the risk score was also proved to be an independent predictor. Among identified 390 candidate SFs, Y-box protein 3 (YBX3) was significantly correlated with OS and metastasis. Among 177 ASEs, ATP-binding cassette subfamily A member 6 (ABCA6)-43162-AT and PLIN5-46808-AT were identified both associated with OS, bone metastasis and co-expressed with SFs. Then we identified primary bile acid biosynthesis as survival-related (KEGG) pathway by Gene Set Variation Analysis (GSVA) and univariate regression analysis, which was correlated with ABCA6-43162-AT and PLIN5-46808-AT. Finally, we proposed that ABCA6-43162-AT and PLIN5-46808-AT may contribute to HCC poor prognosis and metastasis under the regulation of aberrant YBX3 through the pathway of primary bile acid biosynthesis. Portland Press Ltd. 2020-07-15 /pmc/articles/PMC7364508/ /pubmed/32627826 http://dx.doi.org/10.1042/BSR20201001 Text en © 2020 The Author(s). https://creativecommons.org/licenses/by/4.0/ This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY). |
spellingShingle | Bioinformatics Huang, Runzhi Yan, Gaili Sun, Hanlin Zhang, Jie Song, Dianwen Kong, Rui Yan, Penghui Hu, Peng Xie, Aiqing Wang, Siqiao Zhuang, Juanwei Yin, Huabin Meng, Tong Huang, Zongqiang Identification of prognostic and metastasis-related alternative splicing signatures in hepatocellular carcinoma |
title | Identification of prognostic and metastasis-related alternative splicing signatures in hepatocellular carcinoma |
title_full | Identification of prognostic and metastasis-related alternative splicing signatures in hepatocellular carcinoma |
title_fullStr | Identification of prognostic and metastasis-related alternative splicing signatures in hepatocellular carcinoma |
title_full_unstemmed | Identification of prognostic and metastasis-related alternative splicing signatures in hepatocellular carcinoma |
title_short | Identification of prognostic and metastasis-related alternative splicing signatures in hepatocellular carcinoma |
title_sort | identification of prognostic and metastasis-related alternative splicing signatures in hepatocellular carcinoma |
topic | Bioinformatics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7364508/ https://www.ncbi.nlm.nih.gov/pubmed/32627826 http://dx.doi.org/10.1042/BSR20201001 |
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