Expression of hexokinase-2 (HK2), glutaminase-1 (GLS1) and fatty acid synthase (FASN) in gastric cancer and their prognostic significance
Abstract PurposeThe malignant metabolic phenotype characterized by high rates of glycolysis, glutaminolysis and de novo synthesis of fatty acids is also observed in gastric carcinoma. These alterations can be used as therapeutical opportunities with the use of drug inhibitors targeting key enzymes for the metabolism of glucose, glutamine and fatty acid synthesis. MethodsHere we analyzed the immunohistochemical expression of Hexokinase-2 (HK2), Glutaminase-1 (GLS1) and fatty acid synthase (FASN) key enzymes for glycolysis, glutaminolysis and de novo fatty acid synthesis in 92 tumor samples of diffuse gastric carcinoma. Clinicopathological variables, treatment and follow-up data were obtained from files. ResultsHK2 overexpressed in 19 (20.7%), GLS1 in 28 (30.4%) and FASN in 21 (22.8%). Ten (10.9%) patients co-overexpressed HK2/FASN and 8 (8.7%) patients the three enzymes (HK2/GLS1/FASN). Enzyme overexpression either single or combined but no GLS1, correlated with higher stage and disease progression. At a median follow-up time of 31.8 months (2-116). All patients with combined expression died. The co-overexpression of both HK2/FASN and HK2/GLS/FASN was associated with shorter progression free survival whereas only the triple expression with overall survival (median 11.1 vs. 20.4, p=0.01). Nonetheless, stage was the only independent variable for overall survival. ConclusionIn our knowledge, this is the first study to demonstrate that HK2, GLS1 and FASN are concurrently overexpressed which provide support for further studies evaluating the antitumor effects of inhibitors of glycolysis, glutaminolysis and de novo synthesis of fatty acids for metabolic therapy of gastric cancer..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
ResearchSquare.com - (2022) vom: 13. Juni Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
García-Martínez, Elisa [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.21203/rs.3.rs-1743405/v1 |
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| PPN (Katalog-ID): |
XRA036270121 |
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| 520 | |a Abstract PurposeThe malignant metabolic phenotype characterized by high rates of glycolysis, glutaminolysis and de novo synthesis of fatty acids is also observed in gastric carcinoma. These alterations can be used as therapeutical opportunities with the use of drug inhibitors targeting key enzymes for the metabolism of glucose, glutamine and fatty acid synthesis. MethodsHere we analyzed the immunohistochemical expression of Hexokinase-2 (HK2), Glutaminase-1 (GLS1) and fatty acid synthase (FASN) key enzymes for glycolysis, glutaminolysis and de novo fatty acid synthesis in 92 tumor samples of diffuse gastric carcinoma. Clinicopathological variables, treatment and follow-up data were obtained from files. ResultsHK2 overexpressed in 19 (20.7%), GLS1 in 28 (30.4%) and FASN in 21 (22.8%). Ten (10.9%) patients co-overexpressed HK2/FASN and 8 (8.7%) patients the three enzymes (HK2/GLS1/FASN). Enzyme overexpression either single or combined but no GLS1, correlated with higher stage and disease progression. At a median follow-up time of 31.8 months (2-116). All patients with combined expression died. The co-overexpression of both HK2/FASN and HK2/GLS/FASN was associated with shorter progression free survival whereas only the triple expression with overall survival (median 11.1 vs. 20.4, p=0.01). Nonetheless, stage was the only independent variable for overall survival. ConclusionIn our knowledge, this is the first study to demonstrate that HK2, GLS1 and FASN are concurrently overexpressed which provide support for further studies evaluating the antitumor effects of inhibitors of glycolysis, glutaminolysis and de novo synthesis of fatty acids for metabolic therapy of gastric cancer. | ||
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