Low VDAC1 Expression Is Associated with an Aggressive Phenotype and Reduced Overall Patient Survival in Cholangiocellular Carcinoma
| Autor: | Daniel Neureiter, René G. Feichtinger, Ralf Kemmerling, Barbara Kofler, Tobias Kiesslich, Johannes A. Mayr |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male oxidative phosphorylation cholangiocellular carcinoma Oxidative phosphorylation Kaplan-Meier Estimate Mitochondrion Article Cholangiocarcinoma 03 medical and health sciences 0302 clinical medicine energy metabolism medicine Humans Glycolysis lcsh:QH301-705.5 Lymph node Neoplasm Staging Tissue microarray Electron Transport Complex I business.industry Voltage-Dependent Anion Channel 1 Cancer General Medicine medicine.disease Mitochondria 030104 developmental biology medicine.anatomical_structure Phenotype lcsh:Biology (General) Bile Duct Neoplasms 030220 oncology & carcinogenesis Cancer cell Cancer research Female business VDAC1 |
| Zdroj: | Cells Cells, Vol 8, Iss 6, p 539 (2019) Volume 8 Issue 6 |
| ISSN: | 2073-4409 |
| Popis: | Cancer cells frequently exhibit dysfunctional oxidative phosphorylation (OXPHOS) and a concomitant increase in glycolytic flux. We investigated the expression of OXPHOS complex subunits and mitochondrial mass in 34 human cholangiocellular carcinomas (CCCs) and adjacent normal tissue by using tissue microarrays. In the tumor periphery, all OXPHOS complexes were reduced except complex I. In addition, significantly lower levels of complex IV were found at the tumor center (p < 0.0001). Mitochondrial mass, as indicated by VDAC1 expression, was significantly increased in CCCs compared to corresponding normal tissue (p < 0.0001). VDAC1 levels were inversely correlated with UICC (Union Internationale Contre le Cancer) cancer stage classification (p = 0.0065). Furthermore, significantly lower VDAC1 was present in patients with lymph node involvement (p = 0.02). Consistent with this, patients whose carcinomas expressed VDAC1 at low to moderate levels had significantly reduced survival compared to high expressors (p < 0.05). Therefore, low mitochondrial mass is associated with more aggressive CCC. These metabolic features are indicative of a Warburg phenotype in CCCs. This metabolic signature has potential therapeutic implications because tumors with low mitochondrial function may be targeted by metabolic therapies such as a high-fat, low-carbohydrate ketogenic diet. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
| Nepřihlášeným uživatelům se plný text nezobrazuje | K zobrazení výsledku je třeba se přihlásit. |