Glycolytic competence in gastric adenocarcinomas negatively impacts survival outcomes of patients treated with salvage paclitaxel-ramucirumab

Annamaria Ruzzo, Francesco Graziano, Irene Bagaloni, Maria Di Bartolomeo, Michele Prisciandaro, Giuseppe Aprile, Elena Ongaro, Bruno Vincenzi, Giuseppe Perrone, Daniele Santini, Lorenzo Fornaro, Caterina Vivaldi, Gianluca Tomasello, Fotios Loupakis, Sara Lonardi, Matteo Fassan, Michele Valmasoni, Donatella Sarti, Paola Lorenzini, Vincenzo CatalanoRenato Bisonni, Michela Del Prete, Guido Collina, Mauro Magnani

Research output: Contribution to journalArticlepeer-review

Abstract

INTRODUCTION: 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.

MATERIALS AND METHODS: 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.

RESULTS: 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.

CONCLUSIONS: 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.

Original languageEnglish
Pages (from-to)1064-1074
Number of pages11
JournalGastric Cancer
Volume23
Issue number6
DOIs
Publication statusPublished - Nov 2020

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