Promotion of the Warburg effect is associated with poor benefit from adjuvant chemotherapy in colorectal cancer.
Adult
Aged
Antioxidants
/ metabolism
Carbohydrate Metabolism
Chemotherapy, Adjuvant
Colorectal Neoplasms
/ drug therapy
Female
Fluorouracil
/ administration & dosage
Gene Expression Regulation, Neoplastic
/ drug effects
HCT116 Cells
Humans
Male
Middle Aged
Neoplasm Staging
Signal Transduction
/ drug effects
Treatment Outcome
Warburg effect
absolute protein levels
colorectal cancer
relapse risk and chemotherapy benefit
tegafur-uracil
Journal
Cancer science
ISSN: 1349-7006
Titre abrégé: Cancer Sci
Pays: England
ID NLM: 101168776
Informations de publication
Date de publication:
Feb 2020
Feb 2020
Historique:
received:
26
09
2019
revised:
01
12
2019
accepted:
07
12
2019
pubmed:
12
12
2019
medline:
20
2
2020
entrez:
12
12
2019
Statut:
ppublish
Résumé
Metabolic reprogramming, including the Warburg effect, is a hallmark of cancer. Indeed, the diversity of cancer metabolism leads to cancer heterogeneity, but accurate assessment of metabolic properties in tumors has not yet been undertaken. Here, we performed absolute quantification of the expression levels of 113 proteins related to carbohydrate metabolism and antioxidant pathways, in stage III colorectal cancer surgical specimens from 70 patients. The Warburg effect appeared in absolute protein levels between tumor and normal mucosa specimens demonstrated. Notably, the levels of proteins associated with the tricarboxylic citric acid cycle were remarkably reduced in the malignant tumors which had relapsed after surgery and treatment with 5-fluorouracil-based adjuvant therapy. In addition, the efficacy of 5-fluorouracil also decreased in the cultured cancer cell lines with promotion of the Warburg effect. We further identified nine and eight important proteins, which are closely related to the Warburg effect, for relapse risk and 5-fluorouracil benefit, respectively, using a biomarker exploration procedure. These results provide us a clue for bridging between metabolic protein expression profiles and benefit from 5-fluorouracil adjuvant chemotherapy.
Identifiants
pubmed: 31823471
doi: 10.1111/cas.14275
pmc: PMC7004516
doi:
Substances chimiques
Antioxidants
0
Fluorouracil
U3P01618RT
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
658-666Informations de copyright
© 2019 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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