Identification of a Prognostic Index Based on a Metabolic-Genomic Landscape Analysis of Hepatocellular Carcinoma (HCC).

The Cancer Genome Atlas bioinformatical analysis hepatocellular carcinoma metabolic-genomic landscape prognostic index

Journal

Cancer management and research
ISSN: 1179-1322
Titre abrégé: Cancer Manag Res
Pays: New Zealand
ID NLM: 101512700

Informations de publication

Date de publication:
2021
Historique:
received: 26 04 2021
accepted: 05 07 2021
entrez: 23 7 2021
pubmed: 24 7 2021
medline: 24 7 2021
Statut: epublish

Résumé

Metabolic disorders have attracted increasing attention from scientists who conduct research on various tumours, especially hepatocellular carcinoma (HCC). The purpose of this study was to assess the prognostic significance of metabolism in HCC. The expression profiles of metabolism-related genes (MRGs) of 349 surviving HCC patients were extracted from The Cancer Genome Atlas (TCGA) database. Subsequently, a series of biomedical computational algorithms were used to identify a seven-MRG signature as a prognostic model. GSEA indicated the function and pathway enrichment of these MRGs. Then, drug sensitivity analysis was used to identify the hub gene, which was tested using IHC staining. A total of 420 differential MRGs and 116 differentially expressed transcription factors (TFs) were identified in HCC patients based on data from the TCGA database. The GO and KEGG enrichment analyses indicated that metabolic disturbance might be involved in the development of HCC. LASSO regression analysis was used to construct a seven-MRG signature (DHDH, ENO1, G6PD, LPCAT1, PDE6D, PIGU and PPAT) that could predict the prognosis of HCC patients. GSEA revealed the functional and pathway enrichment of these seven MRGs. Then, drug sensitivity analysis indicated that G6PD might play a key role in the prognosis of HCC by promoting chemoresistance. Finally, we used IHC staining to demonstrate the relationship between G6PD expression levels and clinical parameters in HCC patients. The results of this study provide a potential method for predicting the prognosis of HCC patients and avenues for further studies of HCC metabolism. Moreover, the function of G6PD may play a key role in the development and progression of HCC.

Sections du résumé

BACKGROUND BACKGROUND
Metabolic disorders have attracted increasing attention from scientists who conduct research on various tumours, especially hepatocellular carcinoma (HCC). The purpose of this study was to assess the prognostic significance of metabolism in HCC.
METHODS METHODS
The expression profiles of metabolism-related genes (MRGs) of 349 surviving HCC patients were extracted from The Cancer Genome Atlas (TCGA) database. Subsequently, a series of biomedical computational algorithms were used to identify a seven-MRG signature as a prognostic model. GSEA indicated the function and pathway enrichment of these MRGs. Then, drug sensitivity analysis was used to identify the hub gene, which was tested using IHC staining.
RESULTS RESULTS
A total of 420 differential MRGs and 116 differentially expressed transcription factors (TFs) were identified in HCC patients based on data from the TCGA database. The GO and KEGG enrichment analyses indicated that metabolic disturbance might be involved in the development of HCC. LASSO regression analysis was used to construct a seven-MRG signature (DHDH, ENO1, G6PD, LPCAT1, PDE6D, PIGU and PPAT) that could predict the prognosis of HCC patients. GSEA revealed the functional and pathway enrichment of these seven MRGs. Then, drug sensitivity analysis indicated that G6PD might play a key role in the prognosis of HCC by promoting chemoresistance. Finally, we used IHC staining to demonstrate the relationship between G6PD expression levels and clinical parameters in HCC patients.
CONCLUSION CONCLUSIONS
The results of this study provide a potential method for predicting the prognosis of HCC patients and avenues for further studies of HCC metabolism. Moreover, the function of G6PD may play a key role in the development and progression of HCC.

Identifiants

pubmed: 34295189
doi: 10.2147/CMAR.S316588
pii: 316588
pmc: PMC8290353
doi:

Types de publication

Journal Article

Langues

eng

Pagination

5683-5698

Informations de copyright

© 2021 Yang et al.

Déclaration de conflit d'intérêts

The authors report no conflicts of interest in this work.

Références

JAMA Oncol. 2017 Dec 1;3(12):1683-1691
pubmed: 28983565
Acta Biochim Biophys Sin (Shanghai). 2018 Apr 1;50(4):370-380
pubmed: 29471502
Front Oncol. 2020 Aug 13;10:1210
pubmed: 32903581
Liver Int. 2020 Jul;40(7):1756-1769
pubmed: 32174027
Gastroenterology Res. 2009 Aug;2(4):191-199
pubmed: 27942274
Int J Oncol. 2008 Oct;33(4):725-31
pubmed: 18813785
Nat Med. 2004 Apr;10(4):374-81
pubmed: 15034568
Oncotarget. 2016 Mar 1;7(9):10498-512
pubmed: 26871290
Blood. 2014 Jul 3;124(1):134-41
pubmed: 24805191
Eur J Cancer. 2015 Feb;51(3):327-39
pubmed: 25559615
Aging (Albany NY). 2019 Jan 20;11(2):480-500
pubmed: 30661062
Proteomics. 2005 Apr;5(6):1686-92
pubmed: 15800975
Cancer Cell. 2014 Sep 8;26(3):331-343
pubmed: 25132496
Cancer Cell. 2008 Jun;13(6):472-82
pubmed: 18538731
J Hepatol. 2013 Aug;59(2):292-9
pubmed: 23567080
Nat Commun. 2018 Oct 30;9(1):4514
pubmed: 30375513
Nature. 2017 Nov 16;551(7680):340-345
pubmed: 29144460
Hum Pathol. 2019 Jan;83:90-99
pubmed: 30171988
Cancer Res. 2013 Aug 15;73(16):4992-5002
pubmed: 23824744
Nat Rev Gastroenterol Hepatol. 2019 Jul;16(7):411-428
pubmed: 31028350
Cancer Cell. 2012 Mar 20;21(3):297-308
pubmed: 22439925
IUBMB Life. 2012 May;64(5):362-9
pubmed: 22431005
Int J Genomics. 2019 Nov 22;2019:3518378
pubmed: 31886163
Cell. 2019 Oct 31;179(4):829-845.e20
pubmed: 31675496
BMC Med. 2015 Sep 23;13:242
pubmed: 26399231
Science. 2009 May 22;324(5930):1029-33
pubmed: 19460998
Nat Commun. 2019 Jul 29;10(1):3391
pubmed: 31358770
Sci Rep. 2016 Jan 25;6:19763
pubmed: 26805550
Gastroenterology. 2013 May;144(5):1066-1075.e1
pubmed: 23376425
Int J Cancer. 2011 Nov 1;129(9):2226-35
pubmed: 21170963
Sci Rep. 2017 Jan 23;7:41089
pubmed: 28112229
Life Sci. 2020 Jan 15;241:117113
pubmed: 31805288
Exp Ther Med. 2018 Mar;15(3):2777-2785
pubmed: 29599826
Hepat Oncol. 2015 Jul;2(3):209-211
pubmed: 30191000
Cell. 2010 Jan 22;140(2):197-208
pubmed: 20141834
J Endocrinol. 2007 Jun;193(3):445-57
pubmed: 17535882
Bioinformatics. 2018 Nov 1;34(21):3771-3772
pubmed: 29790900
Nature. 2013 Jul 4;499(7456):97-101
pubmed: 23803760
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593

Auteurs

Xin Yang (X)

Department of Infectious Diseases, The First Affiliated Hospital of University of South China, Heng Yang, Hunan, 421000, People's Republic of China.

Qiong Liu (Q)

Department of Infectious Diseases, The First Affiliated Hospital of University of South China, Heng Yang, Hunan, 421000, People's Republic of China.

Juan Zou (J)

Key Laboratory of Tumor Cellular and Molecular Pathology, College of Hunan Province, Cancer Research Institute, University of South China, Hengyang, Hunan, 421001, People's Republic of China.

Yu-Kun Li (YK)

Key Laboratory of Tumor Cellular and Molecular Pathology, College of Hunan Province, Cancer Research Institute, University of South China, Hengyang, Hunan, 421001, People's Republic of China.

Xia Xie (X)

Department of Infectious Diseases, The First Affiliated Hospital of University of South China, Heng Yang, Hunan, 421000, People's Republic of China.

Classifications MeSH