scholarly journals Serum proteomics links suppression of tumor immunity to ancestry and lethal prostate cancer

2021 ◽  
Author(s):  
Tsion Minas ◽  
Julián Candia ◽  
Tiffany Dorsey ◽  
Francine Baker ◽  
Wei Tang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Tumor Immunity ◽  
African American Men ◽  
African Ancestry ◽  
European American ◽  
Serum Proteomics ◽  
Immune Oncology ◽  
Lethal Prostate Cancer ◽  
West African Ancestry

Abstract There is evidence that tumor immunobiology and immunotherapy response may differ between African American and European American prostate cancer patients. Here, we determined if men of African descent harbor a unique systemic immune-oncological signature and measured 82 circulating proteins in almost 3000 Ghanaian, African American, and European American men. Protein signatures for suppression of tumor immunity and chemotaxis were significantly elevated in men of West African ancestry. Importantly, the suppression of tumor immunity protein signature associated with metastatic and lethal prostate cancer, pointing to clinical significance. Moreover, two markers, pleiotrophin and TNFRSF9, predicted poor disease survival specifically among African American men. These findings indicate that immune-oncology marker profiles differ between men of African and European descent. These differences may contribute to the disproportionate burden of lethal prostate cancer in men of African ancestry. The elevated peripheral suppression of tumor immunity may have important implication for guidance of cancer therapy which could particularly benefit African American patients.

scholarly journals Methionine-Homocysteine Pathway in African-American Prostate Cancer

2019 ◽  
Vol 3 (2) ◽  
Author(s):  
Jie H Gohlke ◽  
Stacy M Lloyd ◽  
Sumanta Basu ◽  
Vasanta Putluri ◽  
Shaiju K Vareed ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
Molecular Mechanisms ◽  
Statistical Tests ◽  
African Ancestry ◽  
Tumor Biology ◽  
West African ◽  
Self Report ◽  
European American ◽  
West African Ancestry

Abstract African American (AA) men have a 60% higher incidence and two times greater risk of dying of prostate cancer (PCa) than European American men, yet there is limited insight into the molecular mechanisms driving this difference. To our knowledge, metabolic alterations, a cancer-associated hallmark, have not been reported in AA PCa, despite their importance in tumor biology. Therefore, we measured 190 metabolites across ancestry-verified AA PCa/benign adjacent tissue pairs (n = 33 each) and identified alterations in the methionine-homocysteine pathway utilizing two-sided statistical tests for all comparisons. Consistent with this finding, methionine and homocysteine were elevated in plasma from AA PCa patients using case-control (AA PCa vs AA control, methionine: P = .0007 and homocysteine: P < .0001), biopsy cohorts (AA biopsy positive vs AA biopsy negative, methionine: P = .0002 and homocysteine: P < .0001), and race assignments based on either self-report (AA PCa vs European American PCa, methionine: P = .001, homocysteine: P < .0001) or West African ancestry (upper tertile vs middle tertile, homocysteine: P < .0001; upper tertile vs low tertile, homocysteine: P = .002). These findings demonstrate reprogrammed metabolism in AA PCa patients and provide a potential biological basis for PCa disparities.

scholarly journals Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Walter Rayford ◽  
Alp Tuna Beksac ◽  
Jordan Alger ◽  
Mohammed Alshalalfa ◽  
Mohsen Ahmed ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
African American Men ◽  
Molecular Subtype ◽  
European American ◽  
Beta Catenin ◽  
Expression Of Genes ◽  
Repair Genes ◽  
Clinical Genomic ◽  
Lower Expression

AbstractRacial disparities in prostate cancer have not been well characterized on a genomic level. Here we show the results of a multi-institutional retrospective analysis of 1,152 patients (596 African-American men (AAM) and 556 European-American men (EAM)) who underwent radical prostatectomy. Comparative analyses between the race groups were conducted at the clinical, genomic, pathway, molecular subtype, and prognostic levels. The EAM group had increased ERG (P < 0.001) and ETS (P = 0.02) expression, decreased SPINK1 expression (P < 0.001), and basal-like (P < 0.001) molecular subtypes. After adjusting for confounders, the AAM group was associated with higher expression of CRYBB2, GSTM3, and inflammation genes (IL33, IFNG, CCL4, CD3, ICOSLG), and lower expression of mismatch repair genes (MSH2, MSH6) (p < 0.001 for all). At the pathway level, the AAM group had higher expression of genes sets related to the immune response, apoptosis, hypoxia, and reactive oxygen species. EAM group was associated with higher levels of fatty acid metabolism, DNA repair, and WNT/beta-catenin signaling. Based on cell lines data, AAM were predicted to have higher potential response to DNA damage. In conclusion, biological characteristics of prostate tumor were substantially different in AAM when compared to EAM.

scholarly journals Why do African–American men face higher risks for lethal prostate cancer?

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Sujit S. Nair ◽  
Dimple Chakravarty ◽  
Zachary S. Dovey ◽  
Xiangfu Zhang ◽  
Ashutosh K. Tewari
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
African American Men ◽  
Lethal Prostate Cancer

Abstract PR-11: Blood levels of TNFRSF9 and PTN predict lethal prostate cancer among African American men

2022 ◽  
Author(s):  
Tsion Zewdu Minas ◽  
Julián Candia ◽  
Tiffany H. Dorsey ◽  
Francine Baker ◽  
Wei Tang ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African American ◽  
African American Men ◽  
Blood Levels ◽  
Lethal Prostate Cancer

scholarly journals Understanding the Relationship between Environmental Arsenic and Prostate Cancer Aggressiveness among African-American and European-American Men in North Carolina

2020 ◽  
Vol 17 (22) ◽  
pp. 8364
Author(s):  
Humberto Parada ◽  
Tianying Wu ◽  
Rebecca C. Fry ◽  
Laura Farnan ◽  
Gary J. Smith ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
North Carolina ◽  
African American ◽  
African American Men ◽  
European American ◽  
Total Arsenic ◽  
Cross Sectional ◽  
Low Level ◽  
Cancer Aggressiveness ◽  
Arsenical Species

High-level exposure to arsenic, a known carcinogen and endocrine disruptor, is associated with prostate cancer (PCa) mortality. Whether low-level exposure is associated with PCa aggressiveness remains unknown. We examined the association between urinary arsenic and PCa aggressiveness among men in North Carolina. This cross-sectional study included 463 African-American and 491 European-American men with newly diagnosed, histologically confirmed prostate adenocarcinoma. PCa aggressiveness was defined as low aggressive (Gleason score < 7, stage = cT1–cT2, and PSA < 10 ng/mL) versus intermediate/high aggressive (all other cases). Total arsenic and arsenical species (inorganic arsenic (iAsIII + iAsV), arsenobetaine, monomethyl arsenic, and dimethyl arsenic)) and specific gravity were measured in spot urine samples obtained an average of 23.7 weeks after diagnosis. Multivariable logistic regression was used to estimate the covariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for PCa aggressiveness in association with arsenic tertiles/quantiles overall and by race. The highest (vs. lowest) tertile of total arsenic was associated with PCa aggressiveness ORs of 1.77 (95% CI = 1.05–2.98) among European-American men, and 0.94 (95% CI = 0.57–1.56) among African-American men (PInteraction = 0.04). In contrast, total arsenic and arsenical species were not associated with PCa aggressiveness in unstratified models. Low-level arsenic exposure may be associated with PCa aggressiveness among European-Americans, but not among African-Americans.

Sign in / Sign up

Export Citation Format

Share Document