Large-scale transcriptome profiles reveal robust 20-signatures metabolic prediction models and novel role of G6PC in clear cell renal cell carcinoma.
Biomarkers, Tumor
/ genetics
Carcinoma, Renal Cell
/ genetics
Cohort Studies
Disease Progression
Female
Gene Expression Regulation, Neoplastic
/ genetics
Glucose-6-Phosphatase
/ genetics
Humans
Kidney
/ pathology
Kidney Neoplasms
/ genetics
Male
Prognosis
Transcriptome
/ genetics
Tumor Microenvironment
/ immunology
G6PC
clear cell renal cell carcinoma
immune infiltration
metabolic prediction models
prognosis
tumour microenvironment
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
17
04
2020
revised:
26
05
2020
accepted:
03
06
2020
pubmed:
23
6
2020
medline:
7
5
2021
entrez:
23
6
2020
Statut:
ppublish
Résumé
Clear cell renal cell carcinoma (ccRCC) is the most common and highly malignant pathological type of kidney cancer. We sought to establish a metabolic signature to improve post-operative risk stratification and identify novel targets in the prediction models for ccRCC patients. A total of 58 metabolic differential expressed genes (MDEGs) were identified with significant prognostic value. LASSO regression analysis constructed 20-mRNA signatures models, metabolic prediction models (MPMs), in ccRCC patients from two cohorts. Risk score of MPMs significantly predicts prognosis for ccRCC patients in TCGA (P < 0.001, HR = 3.131, AUC = 0.768) and CPTAC cohorts (P = 0.046, HR = 2.893, AUC = 0.777). In addition, G6PC, a hub gene in PPI network of MPMs, shows significantly prognostic value in 718 ccRCC patients from multiply cohorts. Next, G6Pase was detected high expressed in normal kidney tissues than ccRCC tissues. It suggested that low G6Pase expression significantly correlated with poor prognosis (P < 0.0001, HR = 0.316) and aggressive progression (P < 0.0001, HR = 0.414) in 322 ccRCC patients from FUSCC cohort. Meanwhile, promoter methylation level of G6PC was significantly higher in ccRCC samples with aggressive progression status. G6PC significantly participates in abnormal immune infiltration of ccRCC microenvironment, showing significantly negative association with check-point immune signatures, dendritic cells, Th1 cells, etc. In conclusion, this study first provided the opportunity to comprehensively elucidate the prognostic MDEGs landscape, established novel prognostic model MPMs using large-scale ccRCC transcriptome data and identified G6PC as potential prognostic target in 1,040 ccRCC patients from multiply cohorts. These finding could assist in managing risk assessment and shed valuable insights into treatment strategies of ccRCC.
Identifiants
pubmed: 32567187
doi: 10.1111/jcmm.15536
pmc: PMC7417710
doi:
Substances chimiques
Biomarkers, Tumor
0
Glucose-6-Phosphatase
EC 3.1.3.9
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
9012-9027Informations de copyright
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
Références
Hypertension. 1996 Mar;27(3 Pt 2):723-8
pubmed: 8613231
Proc Natl Acad Sci U S A. 1997 Mar 18;94(6):2145-9
pubmed: 9122162
Cell. 2008 Sep 5;134(5):703-7
pubmed: 18775299
Clin Cancer Res. 2008 Aug 1;14(15):4726-34
pubmed: 18676741
Cancer Cell. 2002 Jun;1(5):459-68
pubmed: 12124175
CA Cancer J Clin. 2020 Jan;70(1):7-30
pubmed: 31912902
Front Oncol. 2018 Dec 18;8:634
pubmed: 30619768
J Transl Med. 2019 Nov 8;17(1):363
pubmed: 31703694
J Cell Mol Med. 2020 Aug;24(16):9012-9027
pubmed: 32567187
J Inherit Metab Dis. 2019 May;42(3):459-469
pubmed: 30637773
Front Plant Sci. 2018 Feb 19;9:190
pubmed: 29515606
Lancet Oncol. 2019 Oct;20(10):1370-1385
pubmed: 31427204
Blood. 2007 May 1;109(9):3812-9
pubmed: 17255361
Nat Rev Clin Oncol. 2019 Jul;16(7):425-441
pubmed: 30914826
Cell. 2015 Sep 10;162(6):1229-41
pubmed: 26321679
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
Semin Cancer Biol. 2009 Feb;19(1):25-31
pubmed: 19130886
Curr Diab Rep. 2009 Jun;9(3):208-14
pubmed: 19490822
PLoS One. 2017 Oct 31;12(10):e0186649
pubmed: 29088295
Eur Urol. 2017 Dec;72(6):962-971
pubmed: 28262413
Clin Cancer Res. 2004 Sep 15;10(18 Pt 2):6290S-5S
pubmed: 15448019
Nat Rev Clin Oncol. 2017 Dec;14(12):717-734
pubmed: 28741618
CA Cancer J Clin. 2019 Sep;69(5):363-385
pubmed: 31184787
Leukemia. 2018 Jul;32(7):1643-1656
pubmed: 29925907
Aging (Albany NY). 2019 Sep 7;11(17):6999-7020
pubmed: 31493764
Eur Urol. 2017 Sep;72(3):368-376
pubmed: 28410865
Cancer Res. 2015 Jun 15;75(12):2541-52
pubmed: 25952651
Mol Cancer. 2006 Nov 24;5:64
pubmed: 17123452
Science. 2010 Sep 17;329(5998):1492-9
pubmed: 20847263
J Cancer. 2019 Jul 10;10(18):4333-4340
pubmed: 31413753
Stem Cell Rev Rep. 2015 Dec;11(6):919-43
pubmed: 26210994
Tumour Biol. 2015 Sep;36(10):7649-58
pubmed: 25926381
Diabetes. 2013 May;62(5):1623-33
pubmed: 23434936
Mol Endocrinol. 2013 Oct;27(10):1632-42
pubmed: 23906633
Cancer Lett. 2020 Aug 10;485:45-55
pubmed: 32428663
Onco Targets Ther. 2019 Apr 17;12:2829-2842
pubmed: 31114230
World J Diabetes. 2017 Jul 15;8(7):317-329
pubmed: 28751954
Mol Cell Proteomics. 2009 May;8(5):971-85
pubmed: 19164279
Neoplasia. 2009 Dec;11(12):1301-8
pubmed: 20019838
Nature. 2017 Jan 18;541(7637):321-330
pubmed: 28102259
J Inherit Metab Dis. 2018 Nov;41(6):955-963
pubmed: 29869165
Cancer. 2017 Dec 15;123(24):4823-4831
pubmed: 28832979
EBioMedicine. 2019 Apr;42:431-442
pubmed: 30935888