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


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.

SUBMITTER: Ruzzo A 

PROVIDER: S-EPMC7567716 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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

Ruzzo Annamaria A   Graziano Francesco F   Bagaloni Irene I   Di Bartolomeo Maria M   Prisciandaro Michele M   Aprile Giuseppe G   Ongaro Elena E   Vincenzi Bruno B   Perrone Giuseppe G   Santini Daniele D   Fornaro Lorenzo L   Vivaldi Caterina C   Tomasello Gianluca G   Loupakis Fotios F   Lonardi Sara S   Fassan Matteo M   Valmasoni Michele M   Sarti Donatella D   Lorenzini Paola P   Catalano Vincenzo V   Bisonni Renato R   Del Prete Michela M   Collina Guido G   Magnani Mauro M  

Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 20200505 6


<h4>Introduction</h4>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.<h4>Materials and methods</h4>Normal mucosa (NM  ...[more]

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