Glycolytic competence in gastric adenocarcinomas negatively impacts survival outcomes of patients treated with salvage paclitaxel-ramucirumab.
Adenocarcinoma
/ metabolism
Aged
Antibodies, Monoclonal, Humanized
/ therapeutic use
Antineoplastic Combined Chemotherapy Protocols
/ therapeutic use
Female
Gastric Mucosa
/ metabolism
Glycolysis
/ genetics
Humans
Male
Mutation
Paclitaxel
/ therapeutic use
RNA, Messenger
/ metabolism
Retrospective Studies
Salvage Therapy
/ mortality
Stomach Neoplasms
/ metabolism
Treatment Outcome
Tumor Suppressor Protein p53
/ genetics
Ramucirumab
Angiogenesis
Glycolysis
Paclitaxel
Ramucirumab
Warburg effect
Journal
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
ISSN: 1436-3305
Titre abrégé: Gastric Cancer
Pays: Japan
ID NLM: 100886238
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
25
02
2020
accepted:
23
04
2020
pubmed:
7
5
2020
medline:
5
8
2021
entrez:
7
5
2020
Statut:
ppublish
Résumé
For energy production, cancer cells maintain a high rate of glycolysis instead of oxidative phosphorylation converting glucose into lactic acid. This metabolic shift is useful to survive in unfavorable microenvironments. We investigated whether a positive glycolytic profile (PGP) in gastric adenocarcinomas may be associated with unfavorable outcomes under an anticancer systemic therapy, including the anti-angiogenic ramucirumab. Normal mucosa (NM) and primary tumor (PT) of 40 metastatic gastric adenocarcinomas patients who received second-line paclitaxel-ramucirumab (PR) were analyzed for mRNA expression of the following genes: HK-1, HK-2, PKM-2, LDH-A, and GLUT-1. Patients were categorized with PGP when at least a doubling of mRNA expression (PT vs. NM) in all glycolytic core enzymes (HK-1 or HK-2, PKM-2, LDH-A) was observed. PGP was also related to TP53 mutational status. Mean LDH-A, HK-2, PKM-2 mRNA expression levels were significantly higher in PT compared with NM. 18 patients were classified as PGP, which was associated with significantly worse progression-free and overall survival times. No significant association was observed between PGP and clinical-pathologic features, including TP53 positive mutational status, in 28 samples. Glycolytic proficiency may negatively affect survival outcomes of metastatic gastric cancer patients treated with PR systemic therapy. TP53 mutational status alone does not seem to explain such a metabolic shift.
Identifiants
pubmed: 32372141
doi: 10.1007/s10120-020-01078-0
pii: 10.1007/s10120-020-01078-0
pmc: PMC7567716
doi:
Substances chimiques
Antibodies, Monoclonal, Humanized
0
RNA, Messenger
0
Tumor Suppressor Protein p53
0
Paclitaxel
P88XT4IS4D
Types de publication
Evaluation Study
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1064-1074Références
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