Morgan L Zenner1, Yves B Helou1, Ryan J Deaton1, Maria Sverdlov1, Heng Wang2,3, Andre Kajdacsy-Balla1,3, Virgilia Macias1, Cindy Voisine4, Marcus Murray5, Sarki A Abdulkadir6, Adam B Murphy6, Larisa Nonn1,3. 1. Department of Pathology, University of Illinois at Chicago, Chicago, Illinois, USA. 2. Department of Epidemiology and Biostatistics, School of Public Health, University of Illinois at Chicago, Chicago, Illinois, USA. 3. Univeristy of Illinois Cancer Center, Chicago, Illinois, USA. 4. Department of Biology, Northeastern Illinois University, Chicago, Illinois, USA. 5. Project Brotherhood, Chicago, Illinois, USA. 6. Department of Urology, Northwestern University, Chicago, Illinois, USA.
Abstract
BACKGROUND: The metabolism of normal prostate relies on glycolysis, with prostate cancer having reduced glycolysis and increased aerobic metabolism. Advanced glycation end products (AGEs) accumulate in tissues as a result of age and glycolytic rate. Differential AGE levels were recently observed in prostate cancer tissues. Herein we sought to quantify AGEs in benign and cancer prostate tissue in a diverse cohort of patients. METHODS: Levels of the AGE Nε-(carboxylethyl)lysine (CML) were quantified by immunohistochemistry (IHC) in a tissue microarray which consisted of 3 cores from tumor and 2 cores from benign areas from 118 patients (87 African American and 31 European American). Ancestry informative markers for African Ancestry were available for 79 patients. Epithelial and stromal areas were quantified separately using an E-cadherin mask. CML levels were compared with clinical grade group and ancestry by mixed linear effect models. Age, prostate-specific antigen (PSA) levels, body mass index (BMI), and hemoglobin A1C were included as covariates. RESULTS: CML levels were lower in areas of the tumor, for both epithelium and surrounding stroma, compared with benign, but did not significantly change with tumor grade group. Age, PSA levels, BMI, and hemoglobin A1C did not associate with CML levels. CML levels were inversely associated with the percentage of African Ancestry in all tissues. CONCLUSIONS: The low CML levels in cancer may reflect the reduced glycolytic state of the tissue. The inverse relationship between African Ancestry and CML levels in both benign and cancer areas suggests a state of reduced glycolysis. It is yet to be determined whether altered glycolysis and CML levels are bystanders or drivers of carcinogenesis.
BACKGROUND: The metabolism of normal prostate relies on glycolysis, with prostate cancer having reduced glycolysis and increased aerobic metabolism. Advanced glycation end products (AGEs) accumulate in tissues as a result of age and glycolytic rate. Differential AGE levels were recently observed in prostate cancer tissues. Herein we sought to quantify AGEs in benign and cancer prostate tissue in a diverse cohort of patients. METHODS: Levels of the AGE Nε-(carboxylethyl)lysine (CML) were quantified by immunohistochemistry (IHC) in a tissue microarray which consisted of 3 cores from tumor and 2 cores from benign areas from 118 patients (87 African American and 31 European American). Ancestry informative markers for African Ancestry were available for 79 patients. Epithelial and stromal areas were quantified separately using an E-cadherin mask. CML levels were compared with clinical grade group and ancestry by mixed linear effect models. Age, prostate-specific antigen (PSA) levels, body mass index (BMI), and hemoglobin A1C were included as covariates. RESULTS: CML levels were lower in areas of the tumor, for both epithelium and surrounding stroma, compared with benign, but did not significantly change with tumor grade group. Age, PSA levels, BMI, and hemoglobin A1C did not associate with CML levels. CML levels were inversely associated with the percentage of African Ancestry in all tissues. CONCLUSIONS: The low CML levels in cancer may reflect the reduced glycolytic state of the tissue. The inverse relationship between African Ancestry and CML levels in both benign and cancer areas suggests a state of reduced glycolysis. It is yet to be determined whether altered glycolysis and CML levels are bystanders or drivers of carcinogenesis.
Authors: François Audenet; François Rozet; Matthieu Resche-Rigon; Rémy Bernard; Alexandre Ingels; Dominique Prapotnich; Rafael Sanchez-Salas; Marc Galiano; Eric Barret; Xavier Cathelineau Journal: Clin Genitourin Cancer Date: 2017-04-26 Impact factor: 2.872
Authors: Mercedes Rodriguez-Teja; Julian H Gronau; Claudia Breit; Yu Zhi Zhang; Ai Minamidate; Matthew P Caley; Afshan McCarthy; Thomas R Cox; Janine T Erler; Luke Gaughan; Steven Darby; Craig Robson; Francesco Mauri; Jonathan Waxman; Justin Sturge Journal: J Pathol Date: 2014-12-24 Impact factor: 7.996