Glycolysis gene expression analysis and selective metabolic advantage in the clinical progression of colorectal cancer
| Autor: | G. De Maglio, P Lorenzini, G. Fiorentini, Chiara Cremolini, Annamaria Ruzzo, Francesco Graziano, Vincenzo Catalano, Mauro Magnani, Federica Zoratto, Giuseppe Aprile, Alfredo Falcone, Elena Ongaro, Eliana Rulli, Fotios Loupakis, Elisa Giacomini, D. Sarti, M De Nictolis, Teresa Ricciardi |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Time Factors Pharmacogenomic Variants Glucose uptake Angiogenesis Inhibitors Kaplan-Meier Estimate Bioinformatics Metastasis 0302 clinical medicine Risk Factors Antineoplastic Combined Chemotherapy Protocols Gene expression Glycolysis Colectomy Regulation of gene expression Liver Neoplasms Gene Expression Regulation Neoplastic Phenotype Treatment Outcome Italy 030220 oncology & carcinogenesis Disease Progression Molecular Medicine Female Colorectal Neoplasms Biology Gene Expression Regulation Enzymologic 03 medical and health sciences Biomarkers Tumor Genetics medicine Hepatectomy Humans Genetic Predisposition to Disease RNA Messenger Aged Retrospective Studies Pharmacology Gene Expression Profiling Metastasectomy medicine.disease Gene expression profiling 030104 developmental biology Drug Resistance Neoplasm Pharmacogenetics Anaerobic glycolysis Mutation Cancer research Pyruvate kinase |
| Popis: | Production of lactate even in the presence of sufficient levels of oxygen (aerobic glycolysis) seems the prevalent energy metabolism pathway in cancer cells. The analysis of altered expression of effectors causing redirection of glucose metabolism would help to characterize this phenomenon with possible therapeutic implications. We analyzed mRNA expression of the key enzymes involved in aerobic glycolysis in normal mucosa (NM), primary tumor (PT) and liver metastasis (LM) of colorectal cancer (CRC) patients (pts) who underwent primary tumor surgery and liver metastasectomy. Tissues of 48 CRC pts were analyzed by RT-qPCR for mRNA expression of the following genes: hexokinase-1 (HK-1) and 2 (HK-2), embryonic pyruvate kinase (PKM-2), lactate dehydrogenase-A (LDH-A), glucose transporter-1 (GLUT-1), voltage-dependent anion-selective channel protein-1 (VDAC-1). Differences in the expression of the candidate genes between tissues and associations with clinical/pathologic features were studied. GLUT-1, LDH-A, HK-1, PKM-2 and VDAC-1 mRNA expression levels were significantly higher in PT/LM tissues compared with NM. There was a trend for higher expression of these genes in LM compared with PT tissues, but differences were statistically significant for LDH-A expression only. RAS mutation-positive disease was associated with high GLUT-1 mRNA expression levels only. Right-sided colon tumors showed significantly higher GLUT-1, PKM-2 and LDH-A mRNA expression levels. High glycolytic profile was significantly associated with poor prognosis in 20 metastatic, RAS-mutated pts treated with first-line chemotherapy plus Bevacizumab. Altered expression of effectors associated with upregulated glucose uptake and aerobic glycolysis occurs in CRC tissues. Additional analyses are warranted for addressing the role of these changes in anti-angiogenic resistance and for developing novel therapeutics. |
| Databáze: | OpenAIRE |
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