Molecular and Immune Features of Metastatic Prostate Cancer in Hispanic and Non‐Hispanic American Men
Alejandro Recio‐Boiles, Sachin Kumar Deshmukh, Cassandra Jean Everly, Sharon Wu, Ricardo J. Estrada‐Mendizabal, Elisabeth Heath, Rana R. McKay, Cynthia Miranti, Ken Batai, Benjamin R. Lee, Juan ChipolliniABSTRACT
Background
Prostate cancer (PCa) is the most common solid tumor in American men, with persistent ethnic disparities, particularly among Hispanic American (HA) men. The tumor microenvironment (TME) and tumor genomics may contribute to disease progression but remain undercharacterized in HA populations.
Methods
We conducted a retrospective exploratory analysis of 83 patients with treatment‐naïve metastatic hormone‐sensitive prostate cancer who underwent next‐generation sequencing (NGS). Tumor genomic alterations, immune profiles, pathway activity, and clinical characteristics were compared between HA and non‐Hispanic White (NHW) patients.
Results
Compared with NHW patients, HA patients presented with higher PSA levels (111.5 vs. 52.6 ng/mL, p = 0.02), and more advanced disease, including T4 tumors (41% vs. 14%, p = 0.01) and visceral metastases (41% vs. 16%, p = 0.04). Pathway analyses identified increased KRAS (FDR = 0.02), Hedgehog (FDR = 0.04), and NOTCH (FDR = 0.07) signaling in HA tumors. HA tumors exhibited higher expression of stem cell markers ( ALDH1A1 , ALDH1A2 , PROM1 ) and immunoinhibitory genes ( PDCD1LG2 , FOXP3 ) (all p < 0.05), along with increased infiltration of M1 macrophages (0.72% vs. 0%) and natural killer (NK) cells (4.84% vs. 3.55%, all p < 0.05 and q < 0.10). HA tumors demonstrated higher expression of genes associated with drug efflux ( ABCC1, ABCB1 ), EMT ( TWIST1, MMP2 ), cell cycle ( CCND2 ), apoptosis inhibition ( BIRC2, XIAP ), and epigenetic regulation ( EP300, TET1, TET2 ) (all p < 0.05 and q < 0.10). Clinically, HA patients initiated therapy earlier (1 vs. 3 months, p ≤ 0.01), had a longer interval to second‐line therapy (20 vs. 11 months, p < 0.05), and had shorter follow‐up (23 vs. 44 months, p = 0.03).
Conclusions
HA patients demonstrated differences in genomic alterations, pathway activity, and tumor immune features compared with NHW patients. Given the study's modest sample size and observational design, these findings should be considered hypothesis‐generating and warrant validation in larger prospective cohorts with broader representation of Hispanic American men.