Cargando…
Eight key long non-coding RNAs predict hepatitis virus positive hepatocellular carcinoma as prognostic targets
BACKGROUND: Hepatitis B virus, together with hepatitis C virus, has been recognized as the leading causes of hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) have been suggested in increasing studies to be the potential prognostic factors for HCC. However, the role of combined applicat...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883184/ https://www.ncbi.nlm.nih.gov/pubmed/31798779 http://dx.doi.org/10.4251/wjgo.v11.i11.983 |
_version_ | 1783474312008695808 |
---|---|
author | Huang, Zi-Lin Li, Wang Chen, Qi-Feng Wu, Pei-Hong Shen, Lu-Jun |
author_facet | Huang, Zi-Lin Li, Wang Chen, Qi-Feng Wu, Pei-Hong Shen, Lu-Jun |
author_sort | Huang, Zi-Lin |
collection | PubMed |
description | BACKGROUND: Hepatitis B virus, together with hepatitis C virus, has been recognized as the leading causes of hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) have been suggested in increasing studies to be the potential prognostic factors for HCC. However, the role of combined application of lncRNAs in estimating overall survival (OS) for hepatitis virus positive HCC (VHCC) is uncertain. AIM: To construct an lncRNA signature related to the OS of VHCC patients to enhance the accuracy of prognosis prediction. METHODS: The expression patterns of lncRNAs, as well as related clinical data were collected from 149 VHCC patients from The Cancer Genome Atlas database. The R package was adopted to obtain the differentially expressed lncRNAs (DElncRNAs). LncRNAs significantly associated with OS were screened by means of univariate Cox regression analysis, so as to construct a least absolute shrinkage and selection operator (LASSO) model. Subsequently, the constructed lncRNA signature was developed and validated. Afterwards, the prognostic nomogram was established, which combined the as-established lncRNA signature as well as the clinical features. Meanwhile, subgroup analysis stratified by the virus type was also performed. Finally, the above-mentioned lncRNAs were enriched to corresponding pathways according to the markedly co-expressed genes. RESULTS: A total of 1420 DElncRNAs were identified, among which 406 were significant in univariate Cox regression analysis. LASSO regression confirmed 8 out of the 406 lncRNAs, including AC005722.2, AC107959.3, AL353803.1, AL589182.1, AP000844.2, AP002478.1, FLJ36000, and NPSR1-AS1. Then, the prognostic risk score was calculated. Our results displayed a significant association between the risk model and the OS of VHCC [hazard ratio = 1.94, 95% confidence interval (CI): 1.61-2.34, log-rank P = 2e-10]. The inference tree suggested that the established lncRNA signature was useful in the risk stratification of VHCC. Furthermore, a nomogram was plotted, and the concordance index of internal validation was 0.763 (95%CI: 0.700-0.826). Moreover, the subgroup analysis regarding etiology confirmed this risk model. In addition, the Wnt signaling pathway, angiogenesis, the p53 pathway, and the PI3 kinase pathway were the remarkably enriched pathways. CONCLUSION: An eight-lncRNA signature has been established to predict the prognosis for VHCC, which contributes to providing a novel foundation for the targeted therapy of VHCC. |
format | Online Article Text |
id | pubmed-6883184 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Baishideng Publishing Group Inc |
record_format | MEDLINE/PubMed |
spelling | pubmed-68831842019-12-03 Eight key long non-coding RNAs predict hepatitis virus positive hepatocellular carcinoma as prognostic targets Huang, Zi-Lin Li, Wang Chen, Qi-Feng Wu, Pei-Hong Shen, Lu-Jun World J Gastrointest Oncol Basic Study BACKGROUND: Hepatitis B virus, together with hepatitis C virus, has been recognized as the leading causes of hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) have been suggested in increasing studies to be the potential prognostic factors for HCC. However, the role of combined application of lncRNAs in estimating overall survival (OS) for hepatitis virus positive HCC (VHCC) is uncertain. AIM: To construct an lncRNA signature related to the OS of VHCC patients to enhance the accuracy of prognosis prediction. METHODS: The expression patterns of lncRNAs, as well as related clinical data were collected from 149 VHCC patients from The Cancer Genome Atlas database. The R package was adopted to obtain the differentially expressed lncRNAs (DElncRNAs). LncRNAs significantly associated with OS were screened by means of univariate Cox regression analysis, so as to construct a least absolute shrinkage and selection operator (LASSO) model. Subsequently, the constructed lncRNA signature was developed and validated. Afterwards, the prognostic nomogram was established, which combined the as-established lncRNA signature as well as the clinical features. Meanwhile, subgroup analysis stratified by the virus type was also performed. Finally, the above-mentioned lncRNAs were enriched to corresponding pathways according to the markedly co-expressed genes. RESULTS: A total of 1420 DElncRNAs were identified, among which 406 were significant in univariate Cox regression analysis. LASSO regression confirmed 8 out of the 406 lncRNAs, including AC005722.2, AC107959.3, AL353803.1, AL589182.1, AP000844.2, AP002478.1, FLJ36000, and NPSR1-AS1. Then, the prognostic risk score was calculated. Our results displayed a significant association between the risk model and the OS of VHCC [hazard ratio = 1.94, 95% confidence interval (CI): 1.61-2.34, log-rank P = 2e-10]. The inference tree suggested that the established lncRNA signature was useful in the risk stratification of VHCC. Furthermore, a nomogram was plotted, and the concordance index of internal validation was 0.763 (95%CI: 0.700-0.826). Moreover, the subgroup analysis regarding etiology confirmed this risk model. In addition, the Wnt signaling pathway, angiogenesis, the p53 pathway, and the PI3 kinase pathway were the remarkably enriched pathways. CONCLUSION: An eight-lncRNA signature has been established to predict the prognosis for VHCC, which contributes to providing a novel foundation for the targeted therapy of VHCC. Baishideng Publishing Group Inc 2019-11-15 2019-11-15 /pmc/articles/PMC6883184/ /pubmed/31798779 http://dx.doi.org/10.4251/wjgo.v11.i11.983 Text en ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. |
spellingShingle | Basic Study Huang, Zi-Lin Li, Wang Chen, Qi-Feng Wu, Pei-Hong Shen, Lu-Jun Eight key long non-coding RNAs predict hepatitis virus positive hepatocellular carcinoma as prognostic targets |
title | Eight key long non-coding RNAs predict hepatitis virus positive hepatocellular carcinoma as prognostic targets |
title_full | Eight key long non-coding RNAs predict hepatitis virus positive hepatocellular carcinoma as prognostic targets |
title_fullStr | Eight key long non-coding RNAs predict hepatitis virus positive hepatocellular carcinoma as prognostic targets |
title_full_unstemmed | Eight key long non-coding RNAs predict hepatitis virus positive hepatocellular carcinoma as prognostic targets |
title_short | Eight key long non-coding RNAs predict hepatitis virus positive hepatocellular carcinoma as prognostic targets |
title_sort | eight key long non-coding rnas predict hepatitis virus positive hepatocellular carcinoma as prognostic targets |
topic | Basic Study |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883184/ https://www.ncbi.nlm.nih.gov/pubmed/31798779 http://dx.doi.org/10.4251/wjgo.v11.i11.983 |
work_keys_str_mv | AT huangzilin eightkeylongnoncodingrnaspredicthepatitisviruspositivehepatocellularcarcinomaasprognostictargets AT liwang eightkeylongnoncodingrnaspredicthepatitisviruspositivehepatocellularcarcinomaasprognostictargets AT chenqifeng eightkeylongnoncodingrnaspredicthepatitisviruspositivehepatocellularcarcinomaasprognostictargets AT wupeihong eightkeylongnoncodingrnaspredicthepatitisviruspositivehepatocellularcarcinomaasprognostictargets AT shenlujun eightkeylongnoncodingrnaspredicthepatitisviruspositivehepatocellularcarcinomaasprognostictargets |