Abstract 1895: Molecular characterization of prostate cancer between Hispanic American and Non-Hispanic Whites: Implications for cancer ethnic health disparities
Authors: Recio-Boiles Alejandro , Deshmukh Sachin Kumar , Chipollini Juan , Batai Ken , Wu Sharon , Xiu Joanne , Farrell Alex , Radovich Milan , Heath Elisabeth , McKay Rana , Nabhan Chadi 
Published: April 2023

Background: Although there is increased awareness leading to early detection and prevention, Hispanic American (HA) men with prostate cancer (PC) continue to have greater mortality rates compared to their Non-Hispanic White (NHW) counterparts. Moreover, HA men with PC are more likely to have more advanced disease compared to NHW men. Here, we characterized the molecular and immune differences in HA and NHW tumors and their association with PC ethnic disparity.

Methods: 88 PC samples (HA=34, NHW=54) obtained from treatment-naive metastatic hormone-sensitive PC (mHSPC) were analyzed by next-generation sequencing (592, NextSeq; WES, NovaSeq), Whole Transcriptome Sequencing (WTS; NovaSeq) (Caris Life Sciences, Phoenix, AZ). AR signature and NEPC score were calculated based on the expression level of previously defined genes (Hieronymus et al. 2006, Beltran et al. 2016). Medical record was reviewed in a deidentified fashion for clinal features. Statistical significance was determined using chi-square and Mann-Whitney U (p&lt;0.05).

Results: HA patients with PC had higher level of PSA (111.5 vs 52.6 ng/ml, p=0.12) and stage (T4: 41% vs 14% p=0.01, M1c: 41% vs 16% p=0.04) but no significant difference in frequency of Gleason score &gt; 4 (79% vs 73%, p=0.61) or stage N1 (69% vs 61%, p=0.85) compared to NHW. HA PC had a significantly higher frequency of TMPRSS2-fusion (46.4% vs 20.0%, p=0.04) compared to NHW PC. By Gene Set Enrichment Analysis, HA PC had enrichment of KRAS signaling (NES: 1.44, FDR=0.02), Hedgehog signaling (NES: 1.45, FDR=0.04), NOTCH signaling (NES: 1.41, FDR=0.07), Hypoxia (NES: 1.38, FDR=0.10) and IL2-STAT5 signaling (NES: 1.35, FDR=0.10) pathways compared to NHW tumors. There was no difference in median Androgen Receptor signature (p=0.78) or Neuroendocrine Prostate Cancer (NEPC) score (p=0.79). Also, no significant difference in AR positivity by IHC (100% vs 95.7%) between HA and NHW PC tumors (p=0.51). HA PC had significantly higher expression of stem cell markers ALDH1A1 (2.1-fold), ALDH1A2 (3-fold), and PROM1 (1.6-fold) and immunoinhibitory genes PDCD1LG2 (1.68-fold) and FOXP3 (1.45-fold) compared to NHW tumors (all p&lt;0.05). Additionally, HA tumors had increased infiltration of M1 Macrophages (0.72% vs 0%) and NK cells (4.84% vs 3.55%, all p&lt;0.05), and increased T-cell inflamed score (44.0 vs -49.0, p=0.14) compared to NHW.

Conclusion: Our data suggest that HA mHSPC is associated with higher levels of PSA, stage, TMPRSS2-fusions, stemness marker expression, immunoinhibitory gene expression, and increased M1 Macrophage and NK cell infiltration. Together, these findings suggest a crucial role of differential molecular and tumor immune microenvironment in PC ethnic disparity. A better understanding of these differences with additional research may help in designing the approaches for reducing the ethnic disparities gaps in PC patients.

Citation Format: Alejandro Recio-Boiles, Sachin Kumar Deshmukh, Juan Chipollini, Ken Batai, Sharon Wu, Joanne Xiu, Alex Farrell, Milan Radovich, Elisabeth Heath, Rana McKay, Chadi Nabhan. Molecular characterization of prostate cancer between Hispanic American and Non-Hispanic Whites: Implications for cancer ethnic health disparities [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 1895.