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Peer-reviewedCC BY 4.0Cancer Reports

Molecular and Immune Features of Metastatic Prostate Cancer in Hispanic and Non‐Hispanic American Men

  • Alejandro Recio‐Boiles1
  • Sachin Kumar Deshmukh2
  • Cassandra Jean Everly1
  • Sharon Wu2
  • Ricardo J. Estrada‐Mendizabal1
  • Elisabeth Heath3
  • Rana R. McKay4
  • Cynthia Miranti1
  • Ken Batai5
  • Benjamin R. Lee1
  • Juan Chipollini1
5 affiliations
  1. 1The University of Arizona Cancer Center Tucson Arizona USA
  2. 2Caris Life Sciences Phoenix Arizona USA
  3. 3Mayo Clinic Rochester Minnesota USA
  4. 4University of California San Diego California USA
  5. 5Roswell Park Comprehensive Cancer Center Buffalo New York USA
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Abstract

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.

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Cite

BibTeXRIS
BibTeX
@article{recioboiles2026molecular,
  title = {{Molecular and Immune Features of Metastatic Prostate Cancer in Hispanic and Non‐Hispanic American Men}},
  author = {Alejandro Recio‐Boiles and Sachin Kumar Deshmukh and Cassandra Jean Everly and Sharon Wu and Ricardo J. Estrada‐Mendizabal and Elisabeth Heath and Rana R. McKay and Cynthia Miranti and Ken Batai and Benjamin R. Lee and Juan Chipollini},
  journal = {Cancer Reports},
  year = {2026},
  month = oct,
  doi = {10.1002/cnr2.70707},
  url = {https://doi.org/10.1002/cnr2.70707},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Molecular and Immune Features of Metastatic Prostate Cancer in Hispanic and Non‐Hispanic American Men
AU  - Alejandro Recio‐Boiles
AU  - Sachin Kumar Deshmukh
AU  - Cassandra Jean Everly
AU  - Sharon Wu
AU  - Ricardo J. Estrada‐Mendizabal
AU  - Elisabeth Heath
AU  - Rana R. McKay
AU  - Cynthia Miranti
AU  - Ken Batai
AU  - Benjamin R. Lee
AU  - Juan Chipollini
PY  - 2026
DA  - 2026/10/01
JO  - Cancer Reports
DO  - 10.1002/cnr2.70707
UR  - https://doi.org/10.1002/cnr2.70707
AB  - 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.
SN  - 2573-8348
ER  -