Development of an Autophagy-Based and Stemness-Correlated Prognostic Model for Hepatocellular Carcinoma Using Bulk and Single-Cell RNA-Sequencing

Accumulating evidence has proved that autophagy serves as a tumor promoter in formed malignancies, and the autophagy-related prognostic signatures have been constructed as clinical tools to predict prognosis in many high-mortality cancers. Autophagy-related genes have participated in the development...

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Autores principales: Shengwei Shen, Rui Wang, Hua Qiu, Chong Li, Jinghan Wang, Junli Xue, Qinghe Tang
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:71d18f4884cc4a02a56be90040c0ab042021-11-08T05:19:02ZDevelopment of an Autophagy-Based and Stemness-Correlated Prognostic Model for Hepatocellular Carcinoma Using Bulk and Single-Cell RNA-Sequencing2296-634X10.3389/fcell.2021.743910https://doaj.org/article/71d18f4884cc4a02a56be90040c0ab042021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.743910/fullhttps://doaj.org/toc/2296-634XAccumulating evidence has proved that autophagy serves as a tumor promoter in formed malignancies, and the autophagy-related prognostic signatures have been constructed as clinical tools to predict prognosis in many high-mortality cancers. Autophagy-related genes have participated in the development and metastasis of hepatocellular carcinoma (HCC), but the understanding of their prognostic value is limited. Thereafter, LIMMA and survival analysis were conducted in both ICGC and TCGA databases and a total of 10 hub autophagy-related genes, namely, NPC1, CDKN2A, RPTOR, SPHK1, HGS, BIRC5, SPNS1, BAK1, ATIC, and MAPK3, were collected. Then, GO, KEGG, correlation, consensus, and PCA analyses were utilized to reveal their potential targeted role in HCC treatment. Single-cell RNA-seq of cancer stem cells also indicated that there was a positive correlation between these genes and stemness. In parallel, we applied univariate, LASSO, and multivariate regression analyses to study the autophagy-related genes and finally proposed that ATIC and BIRC5 were the valuable prognostic indicators of HCC. The signature based on ATIC and BIRC5 exhibited moderate power for predicting the survival of HCC in the ICGC cohort, and its efficacy was further validated in the TCGA cohort. Taken together, we suggested that 10 aforementioned hub genes are promising therapeutic targets of HCC and the ATIC/BIRC5 prognostic signature is a practical prognostic indicator for HCC patients.Shengwei ShenRui WangHua QiuChong LiJinghan WangJunli XueQinghe TangFrontiers Media S.A.articleautophagystemnessATICBIRC5prognosisBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution DOAJ
collection DOAJ
language EN
topic autophagy
stemness
ATIC
BIRC5
prognosis
Biology (General)
QH301-705.5
spellingShingle autophagy
stemness
ATIC
BIRC5
prognosis
Biology (General)
QH301-705.5
Shengwei Shen
Rui Wang
Hua Qiu
Chong Li
Jinghan Wang
Junli Xue
Qinghe Tang
Development of an Autophagy-Based and Stemness-Correlated Prognostic Model for Hepatocellular Carcinoma Using Bulk and Single-Cell RNA-Sequencing
description Accumulating evidence has proved that autophagy serves as a tumor promoter in formed malignancies, and the autophagy-related prognostic signatures have been constructed as clinical tools to predict prognosis in many high-mortality cancers. Autophagy-related genes have participated in the development and metastasis of hepatocellular carcinoma (HCC), but the understanding of their prognostic value is limited. Thereafter, LIMMA and survival analysis were conducted in both ICGC and TCGA databases and a total of 10 hub autophagy-related genes, namely, NPC1, CDKN2A, RPTOR, SPHK1, HGS, BIRC5, SPNS1, BAK1, ATIC, and MAPK3, were collected. Then, GO, KEGG, correlation, consensus, and PCA analyses were utilized to reveal their potential targeted role in HCC treatment. Single-cell RNA-seq of cancer stem cells also indicated that there was a positive correlation between these genes and stemness. In parallel, we applied univariate, LASSO, and multivariate regression analyses to study the autophagy-related genes and finally proposed that ATIC and BIRC5 were the valuable prognostic indicators of HCC. The signature based on ATIC and BIRC5 exhibited moderate power for predicting the survival of HCC in the ICGC cohort, and its efficacy was further validated in the TCGA cohort. Taken together, we suggested that 10 aforementioned hub genes are promising therapeutic targets of HCC and the ATIC/BIRC5 prognostic signature is a practical prognostic indicator for HCC patients.
format article
author Shengwei Shen
Rui Wang
Hua Qiu
Chong Li
Jinghan Wang
Junli Xue
Qinghe Tang
author_facet Shengwei Shen
Rui Wang
Hua Qiu
Chong Li
Jinghan Wang
Junli Xue
Qinghe Tang
author_sort Shengwei Shen
title Development of an Autophagy-Based and Stemness-Correlated Prognostic Model for Hepatocellular Carcinoma Using Bulk and Single-Cell RNA-Sequencing
title_short Development of an Autophagy-Based and Stemness-Correlated Prognostic Model for Hepatocellular Carcinoma Using Bulk and Single-Cell RNA-Sequencing
title_full Development of an Autophagy-Based and Stemness-Correlated Prognostic Model for Hepatocellular Carcinoma Using Bulk and Single-Cell RNA-Sequencing
title_fullStr Development of an Autophagy-Based and Stemness-Correlated Prognostic Model for Hepatocellular Carcinoma Using Bulk and Single-Cell RNA-Sequencing
title_full_unstemmed Development of an Autophagy-Based and Stemness-Correlated Prognostic Model for Hepatocellular Carcinoma Using Bulk and Single-Cell RNA-Sequencing
title_sort development of an autophagy-based and stemness-correlated prognostic model for hepatocellular carcinoma using bulk and single-cell rna-sequencing
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/71d18f4884cc4a02a56be90040c0ab04
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