TY - JOUR
T1 - Advanced glycation end-products (AGEs) are lower in prostate tumor tissue and inversely related to proportion of West African ancestry
AU - Zenner, Morgan L.
AU - Helou, Yves B.
AU - Deaton, Ryan J.
AU - Sverdlov, Maria
AU - Wang, Heng
AU - Kajdacsy-Balla, Andre
AU - Macias, Virgilia
AU - Voisine, Cindy
AU - Murray, Marcus
AU - Abdulkadir, Sarki A.
AU - Murphy, Adam B.
AU - Nonn, Larisa
N1 - Funding Information:
The authors thank Dr. Peter Gann for advice on statistics. Figure 1A was created BioRender. com. This study was funded, in part, by the Department of Defense Prostate Cancer Research Program Health Disparities Idea Award PC170484 (L.N.) and the UIC Center for Clinical and Translation Science Pre‐doctoral Education for Clinical and Translational Scientists (PECTS) Program (M.Z.), the U.S. Department of Veterans Affairs (A.B.M.) grant number IK2CX000926‐01, National Cancer Institute F30CA243197 (M.Z.) and by the National Institutes of Health's National Cancer Institute, grant numbers U54CA202995, U54CA202997, and U54CA203000, known as the Chicago Health Equity Collaborative (L.N., A.B.M., M.M., C.V., and S.A.A.), and National Center for Advancing Translational Sciences UL1TR002002 (H.W.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Defense.
Funding Information:
The authors thank Dr. Peter Gann for advice on statistics. Figure?1A was created BioRender. com. This study was funded, in part, by the Department of Defense Prostate Cancer Research Program Health Disparities Idea Award PC170484 (L.N.) and the UIC Center for Clinical and Translation Science Pre-doctoral Education for Clinical and Translational Scientists (PECTS) Program (M.Z.), the U.S. Department of Veterans Affairs (A.B.M.) grant number IK2CX000926-01, National Cancer Institute F30CA243197 (M.Z.) and by the National Institutes of Health's National Cancer Institute, grant numbers U54CA202995, U54CA202997, and U54CA203000, known as the Chicago Health Equity Collaborative (L.N., A.B.M., M.M., C.V., and S.A.A.), and National Center for Advancing Translational Sciences UL1TR002002 (H.W.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the Department of Defense.
Publisher Copyright:
© 2021 Wiley Periodicals LLC
PY - 2022/2/15
Y1 - 2022/2/15
N2 - 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.
AB - 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.
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U2 - 10.1002/pros.24273
DO - 10.1002/pros.24273
M3 - Article
C2 - 34855273
AN - SCOPUS:85120421647
SN - 0270-4137
VL - 82
SP - 306
EP - 313
JO - Prostate
JF - Prostate
IS - 3
ER -
