Cargando…
Autophagy-Related Gene Pairs Signature for the Prognosis of Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC) has been recognized as the third leading cause of cancer-related deaths worldwide. There is increasing evidence that the abnormal expression of autophagy-related genes plays an important role in the occurrence and development of HCC. Therefore, the study of autophagy-r...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173133/ https://www.ncbi.nlm.nih.gov/pubmed/34095224 http://dx.doi.org/10.3389/fmolb.2021.670241 |
_version_ | 1783702661643632640 |
---|---|
author | Luo, Yiming Liu, Furong Han, Shenqi Qi, Yongqiang Hu, Xinsheng Zhou, Chenyang Liang, Huifang Zhang, Zhiwei |
author_facet | Luo, Yiming Liu, Furong Han, Shenqi Qi, Yongqiang Hu, Xinsheng Zhou, Chenyang Liang, Huifang Zhang, Zhiwei |
author_sort | Luo, Yiming |
collection | PubMed |
description | Hepatocellular carcinoma (HCC) has been recognized as the third leading cause of cancer-related deaths worldwide. There is increasing evidence that the abnormal expression of autophagy-related genes plays an important role in the occurrence and development of HCC. Therefore, the study of autophagy-related genes can further elucidate the genetic drivers of cancer and provide valuable therapeutic targets for clinical treatment. In this study, we used 232 autophagy-related genes extracted from the Human Autophagy Database (HADb) and Molecular Signatures Database (MSigDB) to construct 1884 autophagy-related gene pairs. On this basis, we developed a prognostic model based on autophagy-related gene pairs using least absolute shrinkage and selection operator (LASSO) Cox regression to evaluate the prognosis of patients after liver cancer resection. We then used 845 liver cancer samples from three different databases to test the reliability of the risk signature through survival analysis, receiver operating characteristic (ROC) curve analysis, univariate and multivariate analysis. To further explore the underlying biological mechanisms, we conducted an enrichment analysis of autophagy-related genes. Finally, we combined the signature with independent prognostic factors to construct a nomogram. Based on the autophagy-related gene pair (ARGP) signature, we can divide patients into high- or low-risk groups. Survival analysis and ROC curve analysis verified the validity of the signature (AUC: 0.786—0.828). Multivariate Cox regression showed that the risk score can be used as an independent predictor of the clinical outcomes of liver cancer patients. Notably, this model has a more accurate predictive effect than most prognostic models for hepatocellular carcinoma. Moreover, our model is a powerful supplement to the HCC staging indicator, and a nomogram comprising both indicators can provide a better prognostic effect. Based on pairs of multiple autophagy-related genes, we proposed a prognostic model for predicting the overall survival rate of HCC patients after surgery, which is a promising prognostic indicator. This study confirms the importance of autophagy in the occurrence and development of HCC, and also provides potential biomarkers for targeted treatments. |
format | Online Article Text |
id | pubmed-8173133 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81731332021-06-04 Autophagy-Related Gene Pairs Signature for the Prognosis of Hepatocellular Carcinoma Luo, Yiming Liu, Furong Han, Shenqi Qi, Yongqiang Hu, Xinsheng Zhou, Chenyang Liang, Huifang Zhang, Zhiwei Front Mol Biosci Molecular Biosciences Hepatocellular carcinoma (HCC) has been recognized as the third leading cause of cancer-related deaths worldwide. There is increasing evidence that the abnormal expression of autophagy-related genes plays an important role in the occurrence and development of HCC. Therefore, the study of autophagy-related genes can further elucidate the genetic drivers of cancer and provide valuable therapeutic targets for clinical treatment. In this study, we used 232 autophagy-related genes extracted from the Human Autophagy Database (HADb) and Molecular Signatures Database (MSigDB) to construct 1884 autophagy-related gene pairs. On this basis, we developed a prognostic model based on autophagy-related gene pairs using least absolute shrinkage and selection operator (LASSO) Cox regression to evaluate the prognosis of patients after liver cancer resection. We then used 845 liver cancer samples from three different databases to test the reliability of the risk signature through survival analysis, receiver operating characteristic (ROC) curve analysis, univariate and multivariate analysis. To further explore the underlying biological mechanisms, we conducted an enrichment analysis of autophagy-related genes. Finally, we combined the signature with independent prognostic factors to construct a nomogram. Based on the autophagy-related gene pair (ARGP) signature, we can divide patients into high- or low-risk groups. Survival analysis and ROC curve analysis verified the validity of the signature (AUC: 0.786—0.828). Multivariate Cox regression showed that the risk score can be used as an independent predictor of the clinical outcomes of liver cancer patients. Notably, this model has a more accurate predictive effect than most prognostic models for hepatocellular carcinoma. Moreover, our model is a powerful supplement to the HCC staging indicator, and a nomogram comprising both indicators can provide a better prognostic effect. Based on pairs of multiple autophagy-related genes, we proposed a prognostic model for predicting the overall survival rate of HCC patients after surgery, which is a promising prognostic indicator. This study confirms the importance of autophagy in the occurrence and development of HCC, and also provides potential biomarkers for targeted treatments. Frontiers Media S.A. 2021-05-20 /pmc/articles/PMC8173133/ /pubmed/34095224 http://dx.doi.org/10.3389/fmolb.2021.670241 Text en Copyright © 2021 Luo, Liu, Han, Qi, Hu, Zhou, Liang and Zhang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Biosciences Luo, Yiming Liu, Furong Han, Shenqi Qi, Yongqiang Hu, Xinsheng Zhou, Chenyang Liang, Huifang Zhang, Zhiwei Autophagy-Related Gene Pairs Signature for the Prognosis of Hepatocellular Carcinoma |
title | Autophagy-Related Gene Pairs Signature for the Prognosis of Hepatocellular Carcinoma |
title_full | Autophagy-Related Gene Pairs Signature for the Prognosis of Hepatocellular Carcinoma |
title_fullStr | Autophagy-Related Gene Pairs Signature for the Prognosis of Hepatocellular Carcinoma |
title_full_unstemmed | Autophagy-Related Gene Pairs Signature for the Prognosis of Hepatocellular Carcinoma |
title_short | Autophagy-Related Gene Pairs Signature for the Prognosis of Hepatocellular Carcinoma |
title_sort | autophagy-related gene pairs signature for the prognosis of hepatocellular carcinoma |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173133/ https://www.ncbi.nlm.nih.gov/pubmed/34095224 http://dx.doi.org/10.3389/fmolb.2021.670241 |
work_keys_str_mv | AT luoyiming autophagyrelatedgenepairssignaturefortheprognosisofhepatocellularcarcinoma AT liufurong autophagyrelatedgenepairssignaturefortheprognosisofhepatocellularcarcinoma AT hanshenqi autophagyrelatedgenepairssignaturefortheprognosisofhepatocellularcarcinoma AT qiyongqiang autophagyrelatedgenepairssignaturefortheprognosisofhepatocellularcarcinoma AT huxinsheng autophagyrelatedgenepairssignaturefortheprognosisofhepatocellularcarcinoma AT zhouchenyang autophagyrelatedgenepairssignaturefortheprognosisofhepatocellularcarcinoma AT lianghuifang autophagyrelatedgenepairssignaturefortheprognosisofhepatocellularcarcinoma AT zhangzhiwei autophagyrelatedgenepairssignaturefortheprognosisofhepatocellularcarcinoma |