No abstract

There is evidence that tumor immunobiology and immunotherapy response may differ between African American and European American prostate cancer patients. Here, we determine if men of African descent harbor a unique systemic immune-oncological signature and measure 82 circulating proteins in almost 3000 Ghanaian, African American, and European American men. Protein signatures for suppression of tumor immunity and chemotaxis are elevated in men of West African ancestry. Importantly, the suppression of tumor immunity protein signature associates with metastatic and lethal prostate cancer, pointing to clinical importance. Moreover, two markers, pleiotrophin and TNFRSF9, predict 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.

Background Thromboxane A2 (TXA2) is a platelet- and cyclooxygenase-derived eicosanoid that has been linked to metastasis. We investigated the role of TXA2 in the development of lethal prostate cancer in African American (AA) and European American (EA) men. Methods We measured urinary 11-dehydrothromboxane B2 (TXB2), a stable metabolite of TXA2, with mass-spectrometry. Samples were obtained from 977 cases and 1022 controls at time of recruitment. We applied multivariable logistic and Cox regression modeling to examine associations of TXB2 with prostate cancer and patient survival. Median survival follow-up was 8.4 years with 246 deaths among cases. Aspirin use was assessed with a questionnaire. Race/ethnicity was self-reported. Results Urinary TXB2 was inversely associated with aspirin use. High (> median) TXB2 was associated with prostate cancer in AA (adjusted odds ratio [OR] = 1.50, 95% confidence interval [CI]= 1.13–2.00) but not EA men (OR = 1.07, 95% CI = 0.82–1.40), suggesting upregulated TXA2 synthesis in AA men with prostate cancer. High TXB2 was positively associated with metastatic prostate cancer (OR = 2.60, 95%CI = 1.08–6.28), compared with low (≤ median) TXB2. Furthermore, high TXB2 was also associated with all-cause (adjusted hazard ratio = 1.59, 95% CI = 1.06–2.40) and prostate cancer-specific mortality (hazard ratio = 4.74, 95%CI = 1.62–13.88 in AA men only. Conclusion We report a distinct association of TXB2 with prostate cancer outcomes in AA men. In this high-risk group of men, upregulation of TXA2/TXB2 synthesis may promote metastasis and lethal disease. Our observation identifies a potential benefit of aspirin in preventing lethal prostate cancer through inhibition of TXA2 synthesis.