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Integrated multi-omics analysis identifies ENY2 as a predictor of recurrence and a regulator of telomere maintenance in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has a high recurrence rate. Accurate prediction of recurrence risk is urgently required for tailoring personalized treatment programs for individual HCC patients in advance. In this study, we analyzed a gene expressio...

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Autores principales: Li, Jian-Hua, Tao, Yi-Feng, Shen, Cong-Huan, Li, Rui-Dong, Wang, Zheng, Xing, Hao, Ma, En-Si, Xue, Hong-Yuan, Zhang, Quan-Bao, Ma, Zhen-Yu, Wang, Zheng-Xin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9386066/
https://www.ncbi.nlm.nih.gov/pubmed/35992857
http://dx.doi.org/10.3389/fonc.2022.939948
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author Li, Jian-Hua
Tao, Yi-Feng
Shen, Cong-Huan
Li, Rui-Dong
Wang, Zheng
Xing, Hao
Ma, En-Si
Xue, Hong-Yuan
Zhang, Quan-Bao
Ma, Zhen-Yu
Wang, Zheng-Xin
author_facet Li, Jian-Hua
Tao, Yi-Feng
Shen, Cong-Huan
Li, Rui-Dong
Wang, Zheng
Xing, Hao
Ma, En-Si
Xue, Hong-Yuan
Zhang, Quan-Bao
Ma, Zhen-Yu
Wang, Zheng-Xin
author_sort Li, Jian-Hua
collection PubMed
description Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has a high recurrence rate. Accurate prediction of recurrence risk is urgently required for tailoring personalized treatment programs for individual HCC patients in advance. In this study, we analyzed a gene expression dataset from an HCC cohort with 247 samples and identified five genes including ENY2, GPAA1, NDUFA4L2, NEDD9, and NRP1 as the variables for the prediction of HCC recurrence, especially the early recurrence. The Cox model and risks score were validated in two public HCC cohorts (GSE76427 and The Cancer Genome Atlas (TCGA)) and one cohort from Huashan Hospital, which included a total of 641 samples. Moreover, the multivariate Cox regression analysis revealed that the risk score could serve as an independent prognostic factor in the prediction of HCC recurrence. In addition, we found that ENY2, GPAA1, and NDUFA4L2 were significantly upregulated in HCC of the two validation cohorts, and ENY2 had significantly higher expression levels than another four genes in malignant cells, suggesting that ENY2 might play key roles in malignant cells. The cell line analysis revealed that ENY2 could promote cell cycle progression, cell proliferation, migration, and invasion. The functional analysis of the genes correlated with ENY2 revealed that ENY2 might be involved in telomere maintenance, one of the fundamental hallmarks of cancer. In conclusion, our data indicate that ENY2 may regulate the malignant phenotypes of HCC via activating telomere maintenance.
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spelling pubmed-93860662022-08-19 Integrated multi-omics analysis identifies ENY2 as a predictor of recurrence and a regulator of telomere maintenance in hepatocellular carcinoma Li, Jian-Hua Tao, Yi-Feng Shen, Cong-Huan Li, Rui-Dong Wang, Zheng Xing, Hao Ma, En-Si Xue, Hong-Yuan Zhang, Quan-Bao Ma, Zhen-Yu Wang, Zheng-Xin Front Oncol Oncology Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and has a high recurrence rate. Accurate prediction of recurrence risk is urgently required for tailoring personalized treatment programs for individual HCC patients in advance. In this study, we analyzed a gene expression dataset from an HCC cohort with 247 samples and identified five genes including ENY2, GPAA1, NDUFA4L2, NEDD9, and NRP1 as the variables for the prediction of HCC recurrence, especially the early recurrence. The Cox model and risks score were validated in two public HCC cohorts (GSE76427 and The Cancer Genome Atlas (TCGA)) and one cohort from Huashan Hospital, which included a total of 641 samples. Moreover, the multivariate Cox regression analysis revealed that the risk score could serve as an independent prognostic factor in the prediction of HCC recurrence. In addition, we found that ENY2, GPAA1, and NDUFA4L2 were significantly upregulated in HCC of the two validation cohorts, and ENY2 had significantly higher expression levels than another four genes in malignant cells, suggesting that ENY2 might play key roles in malignant cells. The cell line analysis revealed that ENY2 could promote cell cycle progression, cell proliferation, migration, and invasion. The functional analysis of the genes correlated with ENY2 revealed that ENY2 might be involved in telomere maintenance, one of the fundamental hallmarks of cancer. In conclusion, our data indicate that ENY2 may regulate the malignant phenotypes of HCC via activating telomere maintenance. Frontiers Media S.A. 2022-08-04 /pmc/articles/PMC9386066/ /pubmed/35992857 http://dx.doi.org/10.3389/fonc.2022.939948 Text en Copyright © 2022 Li, Tao, Shen, Li, Wang, Xing, Ma, Xue, Zhang, Ma and Wang 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 Oncology
Li, Jian-Hua
Tao, Yi-Feng
Shen, Cong-Huan
Li, Rui-Dong
Wang, Zheng
Xing, Hao
Ma, En-Si
Xue, Hong-Yuan
Zhang, Quan-Bao
Ma, Zhen-Yu
Wang, Zheng-Xin
Integrated multi-omics analysis identifies ENY2 as a predictor of recurrence and a regulator of telomere maintenance in hepatocellular carcinoma
title Integrated multi-omics analysis identifies ENY2 as a predictor of recurrence and a regulator of telomere maintenance in hepatocellular carcinoma
title_full Integrated multi-omics analysis identifies ENY2 as a predictor of recurrence and a regulator of telomere maintenance in hepatocellular carcinoma
title_fullStr Integrated multi-omics analysis identifies ENY2 as a predictor of recurrence and a regulator of telomere maintenance in hepatocellular carcinoma
title_full_unstemmed Integrated multi-omics analysis identifies ENY2 as a predictor of recurrence and a regulator of telomere maintenance in hepatocellular carcinoma
title_short Integrated multi-omics analysis identifies ENY2 as a predictor of recurrence and a regulator of telomere maintenance in hepatocellular carcinoma
title_sort integrated multi-omics analysis identifies eny2 as a predictor of recurrence and a regulator of telomere maintenance in hepatocellular carcinoma
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9386066/
https://www.ncbi.nlm.nih.gov/pubmed/35992857
http://dx.doi.org/10.3389/fonc.2022.939948
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