STAT3-dependent analysis reveals PDK4 as independent predictor of recurrence in prostate cancer.
Animals
Biomarkers, Tumor
/ genetics
Gene Expression Profiling
/ methods
Gene Expression Regulation, Neoplastic
Humans
Laser Capture Microdissection
Male
Mice
Neoplasm Grading
Neoplasm Recurrence, Local
/ genetics
Neoplasms, Experimental
/ genetics
Oxidative Phosphorylation
Prognosis
Prostatic Neoplasms
/ genetics
Proteomics
/ methods
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
/ genetics
STAT3 Transcription Factor
/ genetics
Systems Biology
Young Adult
OXPHOS
PDK4
STAT3
TCA cycle
prostate cancer
Journal
Molecular systems biology
ISSN: 1744-4292
Titre abrégé: Mol Syst Biol
Pays: England
ID NLM: 101235389
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
19
09
2019
revised:
13
03
2020
accepted:
18
03
2020
entrez:
24
4
2020
pubmed:
24
4
2020
medline:
4
2
2021
Statut:
ppublish
Résumé
Prostate cancer (PCa) has a broad spectrum of clinical behavior; hence, biomarkers are urgently needed for risk stratification. Here, we aim to find potential biomarkers for risk stratification, by utilizing a gene co-expression network of transcriptomics data in addition to laser-microdissected proteomics from human and murine prostate FFPE samples. We show up-regulation of oxidative phosphorylation (OXPHOS) in PCa on the transcriptomic level and up-regulation of the TCA cycle/OXPHOS on the proteomic level, which is inversely correlated to STAT3 expression. We hereby identify gene expression of pyruvate dehydrogenase kinase 4 (PDK4), a key regulator of the TCA cycle, as a promising independent prognostic marker in PCa. PDK4 predicts disease recurrence independent of diagnostic risk factors such as grading, staging, and PSA level. Therefore, low PDK4 is a promising marker for PCa with dismal prognosis.
Identifiants
pubmed: 32323921
doi: 10.15252/msb.20199247
pmc: PMC7178451
doi:
Substances chimiques
Biomarkers, Tumor
0
PDK4 protein, human
0
Pyruvate Dehydrogenase Acetyl-Transferring Kinase
0
STAT3 Transcription Factor
0
STAT3 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e9247Informations de copyright
© 2020 The Authors. Published under the terms of the CC BY 4.0 license.
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