Aldehyde dehydrogenase 1 (ALDH1) isoform expression and potential clinical implications in hepatocellular carcinoma

Cheng Kun Yang; Xiang Kun Wang; Xi Wen Liao; Chuang Ye Han; Ting Dong Yu; Wei Qin; Guang Zhi Zhu; Hao Su; Long Yu; Xiao Guang Liu; Si Cong Lu; Zhi Wei Chen; Zhen Liu; Ke Tuan Huang; Zheng Tao Liu; Yu Liang; Jian Lu Huang; Kai Yin Xiao; Min Hao Peng; Cheryl Ann Winkle; Stephen J. O’Brien; Tao Peng; Stephen James O'Brien

doi:10.1371/journal.pone.0182208

Aldehyde dehydrogenase 1 (ALDH1) isoform expression and potential clinical implications in hepatocellular carcinoma

Cheng Kun Yang
, Xiang Kun Wang
, Xi Wen Liao
, Chuang Ye Han
, Ting Dong Yu
, Wei Qin
, Guang Zhi Zhu
, Hao Su
, Long Yu
, Xiao Guang Liu
, Si Cong Lu
, Zhi Wei Chen
, Zhen Liu
, Ke Tuan Huang
, Zheng Tao Liu
, Yu Liang
, Jian Lu Huang
, Kai Yin Xiao
, Min Hao Peng
, Cheryl Ann Winkle

Stephen J. O’Brien, Tao Peng, Stephen James O'Brien

Research output: Contribution to journal › Article › peer-review

57 Scopus citations

Abstract

Hepatocellular carcinoma (HCC) is one of the most prevalent and life-threatening malignancies worldwide. There are few diagnostic and prognostic biomarkers and druggable targets for HCC. Aldehyde dehydrogenase 1 (ALDH1) is a marker of stem cells in a variety of cancers, but the mRNA levels and prognostic value of ALDH1 isoforms in HCC patients remain unknown. In the present study, gene ontology annotation of the ALDH1 family was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), and the gene pathway analsis was performed using GeneMANIA software. The initial prognostic value of ALDH1 expression in 360 HCC patients was assessed using the OncoLnc database. The expression levels of ALDH1 isoforms in normal liver tissues and clinical specimens of cancer vs. normal control datasets were determined using the GTEx and Oncomine databases, respectively. We then analyzed the prognostic value of ALDH1 expression in 212 hepatitis B virus (HBV)–related HCC patients using the GEO database. We found that the ALDH1 isoform showed high aldehyde dehydrogenase activity. The ALDH1A1, ALDH1B1, and ALDH1L1 genes encoded for the ALDH1 enzyme. High ALDH1B1 expression had protective qualities in HCC patients. Moreover, HBV–related HCC patients who showed high ALDH1L1 gene expression had a better clinical outcomes. In addition, high ALDH1A1 expression was associated with a 57–month recurrence–free survival in HBV-related HCC patients. High ALDH1B1 expression was protective for HCCs with multiple nodules and high serum alpha–fetoprotein (AFP) level. Furthermore, high serum AFP levels contributed to lower ALDH1L1. ALDH1A1, ALDH1B1, and ALDH1L1, all of which were considered promising diagnostic and prognostic markers as well as potential drug targets.

Original language	American English
Article number	e0182208
Journal	PLoS One
Volume	12
Issue number	8
DOIs	https://doi.org/10.1371/journal.pone.0182208
State	Published - Aug 8 2017

Bibliographical note

Publisher Copyright:
© 2017 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding

This work was supported in part by the National Nature Science Foundation of China (No: 81560535, 81072321, 30760243, 30460143 and 30560133), 2009 Program for New Century Excellent Talents in University (NCET), Guangxi Nature Sciences Foundation (No: GuiKeGong 1104003A-7), and Guangxi Health Ministry Medicine Grant (Key-Scientific Research-Grant Z201018).

Funders	Funder number
Guangxi Health Ministry Medicine	Z201018
Guangxi Nature Sciences Foundation	GuiKeGong 1104003A-7
National Nature Science Foundation of China	81560535, 30560133, 81072321, 30760243, 30460143
Program for New Century Excellent Talents in University

ASJC Scopus Subject Areas

General

Keywords

Aldehyde Dehydrogenase 1 Family
Biomarkers, Tumor/metabolism
Carcinoma, Hepatocellular/complications
Datasets as Topic
Disease-Free Survival
Gene Expression Regulation, Neoplastic/physiology
Hepatitis B virus
Hepatitis B/complications
Humans
Isoenzymes/metabolism
Liver Neoplasms/complications
Logistic Models
Prognosis
RNA, Messenger/metabolism
Recurrence
Retinal Dehydrogenase/metabolism
Software

Disciplines

Genetics and Genomics
Life Sciences

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10.1371/journal.pone.0182208

JournalFinal published version, 193 KBLicense: Unspecified

Cite this

Yang, C. K., Wang, X. K., Liao, X. W., Han, C. Y., Yu, T. D., Qin, W., Zhu, G. Z., Su, H., Yu, L., Liu, X. G., Lu, S. C., Chen, Z. W., Liu, Z., Huang, K. T., Liu, Z. T., Liang, Y., Huang, J. L., Xiao, K. Y., Peng, M. H., ... O'Brien, S. J. (2017). Aldehyde dehydrogenase 1 (ALDH1) isoform expression and potential clinical implications in hepatocellular carcinoma. PLoS One, 12(8), Article e0182208. https://doi.org/10.1371/journal.pone.0182208

Yang, CK, Wang, XK, Liao, XW, Han, CY, Yu, TD, Qin, W, Zhu, GZ, Su, H, Yu, L, Liu, XG, Lu, SC, Chen, ZW, Liu, Z, Huang, KT, Liu, ZT, Liang, Y, Huang, JL, Xiao, KY, Peng, MH, Winkle, CA, O’Brien, SJ, Peng, T & O'Brien, SJ 2017, 'Aldehyde dehydrogenase 1 (ALDH1) isoform expression and potential clinical implications in hepatocellular carcinoma', PLoS One, vol. 12, no. 8, e0182208. https://doi.org/10.1371/journal.pone.0182208

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title = "Aldehyde dehydrogenase 1 (ALDH1) isoform expression and potential clinical implications in hepatocellular carcinoma",

abstract = " Hepatocellular carcinoma (HCC) is one of the most prevalent and life-threatening malignancies worldwide. There are few diagnostic and prognostic biomarkers and druggable targets for HCC. Aldehyde dehydrogenase 1 (ALDH1) is a marker of stem cells in a variety of cancers, but the mRNA levels and prognostic value of ALDH1 isoforms in HCC patients remain unknown. In the present study, gene ontology annotation of the ALDH1 family was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), and the gene pathway analsis was performed using GeneMANIA software. The initial prognostic value of ALDH1 expression in 360 HCC patients was assessed using the OncoLnc database. The expression levels of ALDH1 isoforms in normal liver tissues and clinical specimens of cancer vs. normal control datasets were determined using the GTEx and Oncomine databases, respectively. We then analyzed the prognostic value of ALDH1 expression in 212 hepatitis B virus (HBV)–related HCC patients using the GEO database. We found that the ALDH1 isoform showed high aldehyde dehydrogenase activity. The ALDH1A1, ALDH1B1, and ALDH1L1 genes encoded for the ALDH1 enzyme. High ALDH1B1 expression had protective qualities in HCC patients. Moreover, HBV–related HCC patients who showed high ALDH1L1 gene expression had a better clinical outcomes. In addition, high ALDH1A1 expression was associated with a 57–month recurrence–free survival in HBV-related HCC patients. High ALDH1B1 expression was protective for HCCs with multiple nodules and high serum alpha–fetoprotein (AFP) level. Furthermore, high serum AFP levels contributed to lower ALDH1L1. ALDH1A1, ALDH1B1, and ALDH1L1, all of which were considered promising diagnostic and prognostic markers as well as potential drug targets.",

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T1 - Aldehyde dehydrogenase 1 (ALDH1) isoform expression and potential clinical implications in hepatocellular carcinoma

AU - Yang, Cheng Kun

AU - Wang, Xiang Kun

AU - Liao, Xi Wen

AU - Han, Chuang Ye

AU - Yu, Ting Dong

AU - Qin, Wei

AU - Zhu, Guang Zhi

AU - Su, Hao

AU - Yu, Long

AU - Liu, Xiao Guang

AU - Lu, Si Cong

AU - Chen, Zhi Wei

AU - Liu, Zhen

AU - Huang, Ke Tuan

AU - Liu, Zheng Tao

AU - Liang, Yu

AU - Huang, Jian Lu

AU - Xiao, Kai Yin

AU - Peng, Min Hao

AU - Winkle, Cheryl Ann

AU - O’Brien, Stephen J.

AU - Peng, Tao

AU - O'Brien, Stephen James

N1 - Publisher Copyright: © 2017 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

PY - 2017/8/8

Y1 - 2017/8/8

N2 - Hepatocellular carcinoma (HCC) is one of the most prevalent and life-threatening malignancies worldwide. There are few diagnostic and prognostic biomarkers and druggable targets for HCC. Aldehyde dehydrogenase 1 (ALDH1) is a marker of stem cells in a variety of cancers, but the mRNA levels and prognostic value of ALDH1 isoforms in HCC patients remain unknown. In the present study, gene ontology annotation of the ALDH1 family was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), and the gene pathway analsis was performed using GeneMANIA software. The initial prognostic value of ALDH1 expression in 360 HCC patients was assessed using the OncoLnc database. The expression levels of ALDH1 isoforms in normal liver tissues and clinical specimens of cancer vs. normal control datasets were determined using the GTEx and Oncomine databases, respectively. We then analyzed the prognostic value of ALDH1 expression in 212 hepatitis B virus (HBV)–related HCC patients using the GEO database. We found that the ALDH1 isoform showed high aldehyde dehydrogenase activity. The ALDH1A1, ALDH1B1, and ALDH1L1 genes encoded for the ALDH1 enzyme. High ALDH1B1 expression had protective qualities in HCC patients. Moreover, HBV–related HCC patients who showed high ALDH1L1 gene expression had a better clinical outcomes. In addition, high ALDH1A1 expression was associated with a 57–month recurrence–free survival in HBV-related HCC patients. High ALDH1B1 expression was protective for HCCs with multiple nodules and high serum alpha–fetoprotein (AFP) level. Furthermore, high serum AFP levels contributed to lower ALDH1L1. ALDH1A1, ALDH1B1, and ALDH1L1, all of which were considered promising diagnostic and prognostic markers as well as potential drug targets.

AB - Hepatocellular carcinoma (HCC) is one of the most prevalent and life-threatening malignancies worldwide. There are few diagnostic and prognostic biomarkers and druggable targets for HCC. Aldehyde dehydrogenase 1 (ALDH1) is a marker of stem cells in a variety of cancers, but the mRNA levels and prognostic value of ALDH1 isoforms in HCC patients remain unknown. In the present study, gene ontology annotation of the ALDH1 family was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), and the gene pathway analsis was performed using GeneMANIA software. The initial prognostic value of ALDH1 expression in 360 HCC patients was assessed using the OncoLnc database. The expression levels of ALDH1 isoforms in normal liver tissues and clinical specimens of cancer vs. normal control datasets were determined using the GTEx and Oncomine databases, respectively. We then analyzed the prognostic value of ALDH1 expression in 212 hepatitis B virus (HBV)–related HCC patients using the GEO database. We found that the ALDH1 isoform showed high aldehyde dehydrogenase activity. The ALDH1A1, ALDH1B1, and ALDH1L1 genes encoded for the ALDH1 enzyme. High ALDH1B1 expression had protective qualities in HCC patients. Moreover, HBV–related HCC patients who showed high ALDH1L1 gene expression had a better clinical outcomes. In addition, high ALDH1A1 expression was associated with a 57–month recurrence–free survival in HBV-related HCC patients. High ALDH1B1 expression was protective for HCCs with multiple nodules and high serum alpha–fetoprotein (AFP) level. Furthermore, high serum AFP levels contributed to lower ALDH1L1. ALDH1A1, ALDH1B1, and ALDH1L1, all of which were considered promising diagnostic and prognostic markers as well as potential drug targets.

KW - Aldehyde Dehydrogenase 1 Family

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KW - Carcinoma, Hepatocellular/complications

KW - Datasets as Topic

KW - Disease-Free Survival

KW - Gene Expression Regulation, Neoplastic/physiology

KW - Hepatitis B virus

KW - Hepatitis B/complications

KW - Humans

KW - Isoenzymes/metabolism

KW - Liver Neoplasms/complications

KW - Logistic Models

KW - Prognosis

KW - RNA, Messenger/metabolism

KW - Recurrence

KW - Retinal Dehydrogenase/metabolism

KW - Software

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UR - https://www.scopus.com/pages/publications/85027044599#tab=citedBy

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DO - 10.1371/journal.pone.0182208

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SN - 1932-6203

VL - 12

JO - PLoS One

JF - PLoS One

IS - 8

M1 - e0182208

ER -

Aldehyde dehydrogenase 1 (ALDH1) isoform expression and potential clinical implications in hepatocellular carcinoma

Abstract

Bibliographical note

Funding

ASJC Scopus Subject Areas

Keywords

Disciplines

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