Racial Variations in Prostate Cancer Molecular Subtypes and Androgen Receptor Signaling Reflect Anatomic Tumor Location

Abstract

Prostate cancer (PCa) subtypes based on ETS gene expression have been described. Recent studies suggest there are racial differences in tumor location, with PCa located anteriorly more often among African-American (AA) compared to Caucasian-American (CA) men. In this retrospective analysis of a multi-institutional cohort treated by radical prostatectomy (179 CA, 121 AA), we evaluated associations among molecular subtype, race, anatomic tumor location, and androgen receptor (AR) signaling. Subtype (m-ERG+, m-ETS+, m-SPINK1+, or triple-negative) was determined using distribution-based outlier analysis. AR signaling was investigated using gene expression profiling of canonical AR targets. m-ERG+ was more common in CA than AA men (47% vs 22%, p < 0.001). AA men were more likely to be m-SPINK1+ (13% vs 7%; p = 0.069) and triple-negative (50% vs 37%; p = 0.043). Racial differences in molecular subtypes did not persist when tumors were analyzed by location, suggesting a biologically important relationship between tumor location and subtype. Accordingly, anterior tumor location was associated with higher Decipher scores and lower global AR signaling. Patient summary This study demonstrates associations among patient race, prostate cancer molecular subtypes, and tumor location. Location-specific differences in androgen regulation may further underlie these relationships.

Aspirin Use Reduces the Risk of Aggressive Prostate Cancer and Disease Recurrence in African-American Men

“…Our observations are consistent with data showing that AA men have a distinct immune-inflammation signature in their tumors (10, 33–36) and support the hypothesis that aspirin targets inflammation as a driver of disease progression in AA men, thereby reducing lethal prostate cancer in this high-risk group of patients. Recently, a large randomized trial assessing the effects of aspirin on disease recurrence for prostate cancer and other solid cancers has been initiated in the United Kingdom (53).…”

“…Our observation that aspirin, an anti-inflammatory drug, increases disease-free survival among AA patients confirms a similar observation in a previous study (32). These results are quite plausible because earlier data from us and others have shown that prostate tumors in AA men harbor a distinct immune signature (10, 33–36), and measurements of blood CRP showed that AA men tend to have higher CRP levels than EA men (37, 38), indicating increased inflammation, which we confirmed in our study population (Supplementary Figure 1). High blood CRP is associated with an increased prostate cancer mortality although it is neither a marker for disease risk (39–42) nor a good surrogate for the anti-inflammatory effects of aspirin (43, 44).…”

TMPRSS2:ERG fusion gene occurs less frequently in Chinese patients with prostate cancer

“…Recently, similar results were observed in AfricanAmerican and Caucasian-American. Faisal and colleagues demonstrated that higher ERG expression was more common in Caucasian-American patients than African-American, and this difference has been attributed to tumor location in the prostate gland [36]. However, the molecular mechanism of pathways related to the different frequency is unknown yet.…”

The effect of socioeconomic status, race, and insurance type on newly diagnosed metastatic prostate cancer in the United States (2004–2013)

“…We also noted socioeconomic disparities in mPCa were greatest among black and Hispanic men. A number of potential causes for racial disparities have been proposed, ranging from tumor-specific molecular characteristics to social factors such as education and attitudes toward health care [17,18]. In light of these findings, it is important to improve early diagnostic strategies among these vulnerable racial groups.…”