SES AUA 2021: miRNA-301A: A Potential Health Disparity Marker in Men with Prostate Cancer

( Disparities in health care in the United States are widespread and prevalent – racial disparities affecting African Americans are particularly long-standing and consequential. In the context of prostate cancer, it has been long recognized that the incidence is higher among African American men. However, differences in prostate cancer mortality according to race are somewhat less clearly related to underlying biology: while it has been noted that African American men in the United State have higher mortality from prostate cancer than their Caucasian counterparts, these differences are not noted in equal access health care systems such as the Veterans Affairs model.

In a Best of Podium presentation at this year’s Southeast Section of the American Urologic Association Virtual Annual Meeting, Crystal Valadon presented results of their work which aimed to identify genetic factors influencing the disparity among African American patients with prostate cancer, to augment an aggressive marker that can distinguish aggressive cancer from benign prostatic hyperplasia (BPH), and predict biochemical recurrence (BCR) after prostatectomy in African American patients with prostate cancer.

To do so, they utilized 118 serum and 172 tissue samples which were collected from the University of Louisville and VA hospital according to IRB protocols. The authors utilized real-time PCR and immunohistochemistry analyses to quantify the expression of miR-301a and its downstream targets ROCK1 and RUNX3. The authors then examined associations between miR-301a, ROCK1 and RUNX3 expression and on race, Gleason score, and BCR.

They found that miR-301a expression was significantly increased among patients with prostate cancer, compared to those with BPH (p=0.001). Further, assessing the association between miR-301a expression and disease aggressivity, the authors found that miR-301a expression was associated with increasing Gleason score (p=0.001). 

The authors then assessed differences based on race, finding that African American patients with prostate cancer had significantly higher levels of miR-301a expression than Caucasian men (p=0.001). A similar trend was observed in paired needle biopsy specimens from African American men (p=0.008) with a higher Gleason score (p=0.04), which correlated with the aggressiveness of the disease. 

Further, the authors then assessed expression profiles of downstream molecular targets of miR-301a including pro-survival transcription factor ROCK1 and tumor suppressor gene RUNX3. African American men with prostate cancer with higher Gleason scores had higher expression of ROCK1 than their Caucasian counterparts, with an inverse trend observed for RUNX3 expression. The authors further examined prostatectomy specimens finding similar patterns across race-based comparisons. 

The authors conclude that miR-301a expression and downstream signaling are differential between African American and Caucasian patients with prostate cancer and correlate with disease aggressivity. The authors postulate that this biomarker may be useful in clinical decision-making.

Presented by: Crystal Valadon, BS, Student at University of Louisville School of Medicine

Written by: Christopher J.D. Wallis, Urologic Oncology Fellow, Vanderbilt University Medical Center during the 85th Annual Southeastern Section of the American Urological Association, April 23-24, 2021

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